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Archive for the ‘Cancer Prevention: Research & Programs’ Category


Live Notes from Town Hall for Patients with Leading Oncologists on Lung Cancer and COVID19 3_28_20

Reporter: Stephen J. Williams, PhD

UPDATED 3/31/2020

Leading Thoracic Oncologists from the United States and Milan, Italy shared their opinions and views on treating lung cancer patients during this COVID-19 pandemic.  Included in the panel is a thoracic oncologist from Milan Italy who gave special insights into the difficulties and the procedures they are using to help control the spread of infection within this high at-risk patient population and changes to current treatment strategy in light of this current virus outbreak.  Please see live notes and can follow on Twitter at #LungCancerandCOVID19.  Included below is the recording of the Zoom session.

 

UPDATED 3/29/2020

Leading Lung Cancer Oncologists from around the world are meeting and discussing concerns for lung cancer patients and oncologist during the novel coronavirus (SARS-COV2; COVID19) pandemic.  The town hall “COVID-19 and the Impact on Thoracic Oncology” will be held on Zoom on Saturday March 28, 2020 at 10:00 – 11:30 AM EST. sponsored by Axiom Healthcare Strategies . You can register at

Please join this virtual Town Hall

Zoom link: https://us04web.zoom.us/j/846752048

Zoom Webinar ID: 846-752-048

eSpeakers

Anne Chiang, MD, PhD, Associate Professor; Chief Network Officer and Deputy Chief Medical Officer, Smilow Cancer Network

Roy S. Herbst, MD, PhD, Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology; Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Associate Cancer Center Director for Translational Research, Yale Cancer Center

 Kurt Schalper, MD, PhD Assistant Professor of Pathology; Director, Translational Immuno-oncology Laboratory

Martin J. Edelman, MD, Chair, Department of Hematology/Oncology, Fox Chase Cancer Center

Corey J. Langer, MD , Professor of Medicine, University of Pennsylvania

Hossain Borghaei, DO, MS , Chief of Thoracic Medical Oncology and Director of Lung Cancer Risk Assessment, Fox Chase Cancer Center

Marina Garassino, MD, Fondazione IRCCS Instituto Nazionale del Tumori

Kristen Ashley Marrone, MD, Thoracic Medical Oncologist. Johns Hopkins Bayview Medical Center

Taofeek Owonikoko, MD, PhD, MSCR, Medical Oncologist, Emory University School of Medicine

Jeffrey D. BradleyMD, FACR, FASTRO , Emory University School of Medicine

Brendon Stiles, M.D, Weil Cornell

@pharma_BI will be Live Tweeting in Real Time this Town Hall

Please follow at the following # (hashtags)

#LungCancerandCOVID19

#Livingwithcancer

#LungCancer

#NoOneAlone

and

UPDATED 3/29/2020

Below is a collection of live Tweets from this meeting as well as some notes and comments from each of the speakers and panelists.  The recording of this Town Hall will be posted on this site when available.  The Town Hall was well attended with over 250 participants

Town Hall Notes

The following represent some notes taken at this Town Hall.

Dr. Owonkiko: 1-2% lethality in China; for patients newly diagnosed with lung cancer 1) limit contact between patient, physician and healthcare facility = telemedicine and oral chemo suggested 2) for immunotherapy if i.v. must monitor health carefully

Dr. Kurt Schalper: on COVID19 testing: Three types of tests each having pros and cons.

  •     viral culture: not always practical as you need lots of specimen
  • ELISA: looking for circulating antibodies but not always specific for type of coronavirus
  • RT-PCR: most sensitive but right now not much clarity on best primers to use; he noted that there is a 15% variance in test results using different primers to different targeted COVID19 genes

Dr. Marina Garassino: The Lombardi outbreak was 1st in Italy and took them by surprise.  She admits they were about one month behind in preparation where they did not have enough masks as late as January 31.  It was impractical to socially distance given Italian customs in greeting each other.  In addition, they had to determine which facilities would be COVID negative and COVID positive an this required access to testing.  Right now they are only testing symptomatic patients and healthcare workers have to test negative multiple times.  As concerning therapy with lung cancer patients, they have been delaying as much as possible the initiation of therapy.  Patients that are on immunotherapy and immunosuppresive drugs are being monitored by CT scan more often during this pandemic so as instances of pneumotitis began increasing they were unsure if these patients are at increased risk of infection to COVID19 or just a bias in that they are screening more often so their risk to COVID 19 is unclear.  Dr. Garissino also felt we need to move from hospital based to community based measures of prevention against COVID infection (social distancing, citizens more vigilant).  She noted that usually the cancer patients are more careful with respect to preventative measures than the general populace.  Healthcare workers have to test negative twice in three days if they had been in close contact with a COVID postitive patient.  However her hospital is still running at 80% capacity so patients are getting treated. However there are ethical issues as to who gets treated, who gets respirators, and other ethical issues related to unfortunate rationing of care.

Dr. Anne Chiang: Scheduled visits have notably decreased.  They have seen patients visits decrease from 4500 down to 2300 in two weeks but telemedicine visits or virtual visits have increased to 1000 so are replacing the on site visits.  She also said they are trying to reduce or eliminate the extremely immuno-suppressive drugs from chemotherapy regimens.  For example they are removing pemetrexemed from standard regimens and also considering neoadjuvant chemotherapy.  As far as biopsies, liquid biopsies can be obtained in the home so more preferred as patients do not have to come in for biopsy.

Dr. Edelman: Fox Chase is somewhat unique in being an NCI center which only does oncology so they rely on neighboring Jeanes Hospital of the Temple University Health System for a lot of their outpatient and surgical and general medicine needs.  Patients who will be transferred back to Fox Chase are screened for COVID19.

Brenden Stiles: Lung cancer surgeries have ground to a halt.  He did only one last week.  The hospital wants to conserve resources and considers lung cancer surgery to great a COVID risk.  They have shut down elective surgeries and there are no clinical trials being conducted.  He said that lung cancer research will be negatively impacted by the pandemic as resources are shuttled to COVID research efforts.

 Live Tweets

 

Other article of note on Coronavirus (COVID19) please see our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

 

 

 

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Responses to the #COVID-19 outbreak from Oncologists, Cancer Societies and the NCI: Important information for cancer patients

Curator: Stephen J. Williams, Ph.D.

UPDATED 3/20/2020

Among the people who are identified at risk of coronovirus 2019 infection and complications of the virus include cancer patients undergoing chemotherapy, who in general, can be immunosuppressed, especially while patients are undergoing their treatment.  This has created anxiety among many cancer patients as well as their care givers and prompted many oncologist professional groups, cancer societies, and cancer centers to formulate some sort of guidelines for both the cancer patients and the oncology professional with respect to limiting the risk of infection to coronavirus (COVID19). 

 

This information will be periodically updated and we are working to get a Live Twitter Feed to bring oncologist and cancer patient advocacy groups together so up to date information can be communicated rapidly.  Please see this page regularly for updates as new information is curated.

IN ADDITION, I will curate a listing of drugs with adverse events of immunosuppression for people who might wonder if the medications they are taking are raising their risk of infections.

Please also see @pharma_BI for updates as well.

Please also see our Coronavirus Portal at https://pharmaceuticalintelligence.com/coronavirus-portal/

For ease of reading information for patients are BOLDED and in RED

ASCO’s Response to COVID-19

From the Cancer Letter: The following is a guest editorial by American Society of Clinical Oncology (ASCO) Executive Vice President and Chief Medical Officer Richard L. Schilsky MD, FACP, FSCT, FASCO. This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.

 

The worldwide spread of the coronavirus (COVID-19) presents unprecedented challenges to the cancer care delivery system.

Our patients are already dealing with a life-threatening illness and are particularly vulnerable to this viral infection, which can be even more deadly for them. Further, as restrictions in daily movement and social distancing take hold, vulnerable patients may be disconnected from friends, family or other support they need as they manage their cancer.

As providers, we rely on evidence and experience when treating patients but now we face uncertainty. There are limited data to guide us in the specific management of cancer patients confronting COVID-19 and, at present, we have no population-level guidance regarding acceptable or appropriate adjustments of treatment and practice operations that both ensure the best outcome for our patients and protect the safety of our colleagues and staff.

As normal life is dramatically changed, we are all feeling anxious about the extreme economic challenges we face, but these issues are perhaps even more difficult for our patients, many of whom are now facing interruption

As we confront this extraordinary situation, the health and safety of members, staff, and individuals with cancer—in fact, the entire cancer community—is ASCO’s highest priority.

ASCO has been actively monitoring and responding to the pandemic to ensure that accurate information is readily available to clinicians and their patients. Recognizing that this is a rapidly evolving situation and that limited oncology-specific, evidence-based information is available, we are committed to sharing what is known and acknowledging what is unknown so that the most informed decisions can be made.

To help guide oncology professionals as they deal with the impact of coronavirus on both their patients and staff, ASCO has collated questions from its members, posted responses at asco.org and assembled a compendium of additional resources we hope will be helpful as the virus spreads and the disease unfolds. We continue to receive additional questions regarding clinical care and we are updating our FAQs on a regular basis.

We hope this information is helpful even when it merely confirms that there are no certain answers to many questions. Our answers are based on the best available information we identify in the literature, guidance from public health authorities, and input received from oncology and infectious disease experts.

For patients, we have posted a blog by Dr. Merry Jennifer Markham, chair of ASCO’s Cancer Communications Committee. This can be found on Cancer.Net, ASCO’s patient information website, and it provides practical guidance to help patients reduce their risk of exposure, better understand COVID-19 symptoms, and locate additional information.

This blog is available both in English and Spanish. Additional blog posts addressing patient questions will be posted as new questions are received and new information becomes available.

Find below a Tweet from Dr.Markham which includes links to her article on COVID-19 for cancer patients

https://twitter.com/DrMarkham/status/1237797251038220289?s=20

NCCN’s Response to COVID-19 and COVID-19 Resources

JNCCN: How to Manage Cancer Care during COVID-19 Pandemic

Experts from the Seattle Cancer Care Alliance (SCCA)—a Member Institution of the National Comprehensive Cancer Network® (NCCN®)—are sharing insights and advice on how to continue providing optimal cancer care during the novel coronavirus (COVID-19) pandemic. SCCA includes the Fred Hutchinson Cancer Research Center and the University of Washington, which are located in the epicenter of the COVID-19 outbreak in the United States. The peer-reviewed article sharing best practices is available for free online-ahead-of-print via open access at JNCCN.org.

Coronavirus disease 2019 (COVID-19) Resources for the Cancer Care Community

NCCN recognizes the rapidly changing medical information relating to COVID-19 in the oncology ecosystem, but understands that a forum for sharing best practices and specific institutional responses may be helpful to others.  Therefore, we are expeditiously providing documents and recommendations developed by NCCN Member Institutions or Guideline Panels as resources for oncology care providers. These resources have not been developed or reviewed by the standard NCCN processes, and are provided for information purposes only. We will post more resources as they become available so check back for additional updates.

Documents

Links

National Cancer Institute Response to COVID-19

More information at https://www.cancer.gov/contact/emergency-preparedness/coronavirus

What people with cancer should know: https://www.cancer.gov/coronavirus

Get the latest public health information from CDC: https://www.coronavirus.gov

Get the latest research information from NIH: https://www.nih.gov/coronavirus

 

Coronavirus: What People with Cancer Should Know

ON THIS PAGE

Both the resources at cancer.gov (NCI) as well as the resources from ASCO are updated as new information is evaluated and more guidelines are formulated by members of the oncologist and cancer care community and are excellent resources for those living with cancer, and also those who either care for cancer patients or their family and relatives.

Related Resources for Patients (please click on links)

 

 

 

Some resources and information for cancer patients from Twitter

Twitter feeds which may be useful sources of discussion and for cancer patients include:

 

@OncLive OncLive.com includes healthcare information for patients and includes videos and newsletters

 

 

@DrMarkham Dr. Markham is Chief of Heme-Onc & gyn med onc @UF | AD Med Affairs @UFHealthCancer and has collected very good information for patients concerning #Covid19 

 

 

@DrMaurieMarkman Dr. Maurie Markman is President of Medicine and Science (Cancer Centers of America, Philadelphia) @CancerCenter #TreatThePerson #Oncology #Genomics #PrecisionMedicine and hosts a great online live Tweet feed discussing current topics in cancer treatment and care for patients called #TreatThePerson Chat

UPDATED 3/20/2020 INFORMATION FROM NCI DESIGNATED CANCER CENTERS FOR PATIENTS/PROVIDERS

The following is a listing with links of NCI Designated Comprehensive Cancer Centers and some select designated Cancer Centers* which have information on infectious risk guidance for cancer patients as well as their physicians and caregivers.   There are 51 NCI Comprehensive Cancer Centers and as more cancer centers formulate guidance this list will be updated. 

 

Cancer Center State Link to COVID19 guidance
City of Hope CA Advice for cancer patients, survivors and caregivers
Jonsson Cancer Center at UCLA CA Cancer and COVID19
UCSF Hellen Diller Family Comprehensive Cancer CA COVID-19 Links for Patients and Providers
Lee Moffit FL Protecting against Coronavirus 19
University of Kansas Cancer Center* KS COVID19 Info for patients
Barbara & Karmanos Cancer Institute (Wayne State) MI COVID19 Resources
Rogel Cancer Center (Univ of Michigan) MI COVID19 Patient Specific Guidelines
Alvin J. Siteman Cancer Center (MO) Coronavirus
Fred & Pamela Buffet CC* NE Resources for Patients and Providers
Rutgers Cancer Institute of NJ NJ What patients should know about COVID19
Memorial Sloan Kettering NY What COVID19 means for cancer patients
Herbert Irving CC (Columbia University) NY Coronavirus Resource Center
MD Anderson Cancer  TX Planning for Patients, Providers
Hunstman Cancer Center UT COVID19 What you need to know
Fred Hutchinson WA COVID19 What patients need to know

 

 

Please also see related information on Coronavirus 2019 and Cancer and Immunotherapy at the following links on the Open Access Online Journal:

Volume Two: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery 

at

https://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/volume-two-immunotherapy-in-cancer-radiation-oncology/

AND

Coronavirus Portal

 

 

 

 

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The Sylvester Comprehensive Cancer Center of the University of Miami named 71st NCI designated Cancer Center

 

Reporter: Stephen J. Williams, PhD

As seen in the Cancer Letter at https://cancerletter.com/articles/20190729_1/

Conversation with The Cancer Letter

Sylvester becomes 71st NCI-designated cancer center

Stephen Nimer

Director,

Sylvester Comprehensive Cancer Center

 

After six years of  aggressively recruiting and spending more than $250 million to build up its programs, Sylvester Comprehensive Cancer Center has become the 71st NCI-designated cancer center in the US and the only such institution in South Florida.

The designation was announced July 29.

Sylvester, which is a part of the University of Miami Leonard M. Miller School of Medicine, is one of 64 cancer centers with the NCI Cancer Center designation in the nation. Fifty of these centers hold the Comprehensive Cancer Center designation. Seven more are designated as Basic Laboratory Cancer Centers.

“There are over 21 million people who live in the state of Florida. In 2014, Florida became the third largest state in the United States, surpassing New York—yet New York has seven NCI designated cancer centers and Florida had had only one,” Stephen D. Nimer, director of Sylvester, said to The Cancer Letter.

“There are over six million people in our catchment area, South Florida, and if they wanted to go to an NCI-designated cancer center they’d have to either get on a plane or drive nearly 300 miles—to Tampa.”

Public health programs that helped Sylvester secure the NCI designation include the Game Changer vehicle, which brings evidence-based interventions to underserved communities in the cancer center’s catchment area (The Cancer Letter, April 27, 2018). The center’s cancer control program also includes the Firefighter Cancer Initiative, a long-term study of exposures to carcinogens and ways to reduce and prevent cancer risks for Florida firefighters.

 

 

The cancer center is working on deploying another Game Changer vehicle. Recently, Peter Tunney, a New York and Miami-based artist and gallerist who donated a painting for the first Game Changer van, donated another painting that Sylvester can sell to raise money for its programs (The Cancer Letter, April 27, 2018).

 

“When they got that designation, they were walking on sunshine,” Tunney said to The Cancer Letter. “I think it’s a universal idea. I think that’s the goal for all of us—for all of mankind, for sick and healthy—to have that feeling that is so rare today: I am walking on sunshine. It’s almost like a thing of the past. Who can walk on sunshine today, in this crazy world filled with suffering and illness? And I just feel like we can, we can, it’s possible to be grateful for the things we have.

The intense yellow wallpaper motif reminds Tunney of the wallpaper in his grandmother’s house in the 1960s and 1970s, the time when American astronauts walked on the moon. “It’s somebody’s grandmother’s wallpaper from the sixties. We look back at that time, we look back at landing on the moon, and everyone is aflutter, ‘Oh, those were the good old days.’ No, these are the good old days.”

The word “comprehensive” in Sylvester’s name doesn’t refer to its level of NCI designation. When it was founded in 1973, the institution was known as the Comprehensive Cancer Center for the State of Florida. In 1992, after receiving a $27.5 million gift from the philanthropist Harcourt Sylvester Jr., it was renamed Sylvester Comprehensive Cancer Center.

 

Sylvester director Nimer spoke with Paul Goldberg, editor and publisher of The Cancer Letter.

 

Paul Goldberg:

First of all, congratulations.

Stephen Nimer: 

Thank you; it’s a big deal.

 

PG:

How long did it take to get this done?

SN:

I’d say, six years. I arrived in 2012, seven years ago, and the first year started by assessing what’s going on at Sylvester. We then developed our first five-year strategic plan, which ran from 2014 to 2018, and we submitted our [Cancer Center Support Grant] application in September 2018. We’re now in the midst of our second five-year plan.

 

PG:

And how much money did it require?

SN:

I’d have to add it all up. One of the most important things for us was that the state, in 2014, started giving us a bit over $16 million a year so that we could become NCI-designated. The health system, over a five-to-six-year period, probably gave us somewhere between $90 and $100 million. And then we’ve raised philanthropy. The philanthropy over five to six years, is maybe close to $100 million. So, it’s probably $250 -$270 million.

 

PG:

How many people did you have to recruit?

SN:

We went in [to NCI] with 124 members on our CCSG application, but over the last seven years we’ve recruited nearly 150 people. In addition to recruiting researchers I’ve been given the opportunity to build the clinical programs also.

Many of the clinical people are not included on the grant, because the grant has very specific requirements to be a member. For example, we’ve hired a couple of breast cancer surgeons, and they are not listed on the grant, because they are not yet doing significant research.

The NCI doesn’t want to know about people who don’t have grants or aren’t running clinical trials. So, out of the 124, which is what we went in with, I believe nearly 50 of our members were new.

 

PG:

How is your cancer center different from all others?

SN:

One of the things that we got the highest marks on is our community outreach and engagement efforts and how relevant the research we’re doing is to our catchment area.

A couple of examples:

We have a West Indies population, so we have an endemic HTLV-1-infected population, and thus a significant number of HTLV-1-related adult T-cell leukemia patients. So, one of our physician scientists has an R01 studying ATL. And we have a number of clinical trials for people with adult T-cell leukemia.

We also have a large burden of advanced cervical cancer patients in our region, especially in Little Haiti. And so, we have a lot of efforts on early detection of high-risk HPV, prevention and clinical treatment trials for women with cervical cancer.

Another thing that distinguishes us from many centers is the diversity of our faculty, our students, and the patients we put on clinical trials. In our CCSG application, roughly 30% of the patients on interventional trials were black and 40% were Hispanic—so both racial and ethnic diversity. We also have incredible socio-economic diversity.

What’s unique among the black population in our catchment area is that it is Afro-Caribbean more than African American—different genetics, different cultures.

The Hispanic population is unique as well. MD Anderson is probably largely Mexican Americans. New York is probably mostly Dominican and Puerto Rican. We have significant populations of Cuban Americans, Venezuelans, Brazilians, Argentinians, Colombians—an incredibly diverse group.

One example of how this plays out is in our prostate cancer research. The watch-and-wait approach is an appropriate strategy for many people. We found that our black population has more anterior prostate cancer lesions, so when you do blind biopsies, you’re more likely to miss lesions.

And then we’ve looked among the Hispanic populations as to who has a better or worse prognosis and we’ve identified subgroups within the Hispanic population that have different genetics and a different biology. So, we are tailoring our approach. Based on genetic ancestry as well as other factors.

The other thing is, we have a very strong cancer epigenetics programs, a very strong program on infections and cancer, including H. Pylori, HPV, and hepatitis viruses B and C.

We are very focused on developing programs that meet the needs of the people in this six-million-plus community.

Our catchment area is four counties, somewhat famous, because of the election news nearly every cycle: Broward, Palm Beach County, Miami Dade and Monroe County.

 

PG:

New York, where you come from, has an NCI-designated cancer center on every street corner. And Miami—make that South Florida—has just one now. How is Florida different? You would have thought that there would be multiple NCI-designated cancer centers in South Florida.

SN:

Your point is very well taken. There are over 21 million people who live in the state of Florida. In 2014, Florida became the third largest state in the United States, surpassing New York—yet New York has seven NCI designated cancer centers and Florida had had only one.

Moffitt had gotten a huge investment from the state in the past, and that enabled them to become NCI-designated. And upon designation, they could recruit more researchers, attract more patients, and get more philanthropy, and get all the positives from that. And for the longest time, Florida has only had one.

There are over six million people in our catchment area, South Florida, and if they wanted to go to an NCI-designated cancer center they’d have to either get on a plane or drive nearly 300 miles—to Tampa.

Now, one problem that we face in our region, which is very splintered in terms of market share, etc. is that there’s a lot of community hospitals here that have cancer centers, but they are not necessarily conducting cancer research in any way.

I’ve been reading Joe Simone’s Journal of Clinical Oncology paper from 2002, where he talks about the fact that there are no criteria to call yourself a cancer center. And because people may feel like you can get great care anywhere, they may not seek out the experts.

Probably, in many markets throughout the US, there’s still an ongoing process of trying to educate people as to what’s the difference between an NCI-designated cancer center and one that’s not. And, obviously, the designation is given, because of the research that’s going on. And so, people wonder: “What is the connection between the research and me being a patient there?”

A big part of educating our community is to tell people that oftentimes the doctors who are doing research on a specific cancer have a deeper knowledge about its management. Also, experts more often make the correct diagnosis and come up with more exact multidisciplinary treatment approaches for many cancers.

NCI-designated cancer centers have more clinical trials and more investigator-initiated clinical trials. Now, with NCI designation, we’ll have access to the [NCI Cancer Therapy Evaluation Program] drugs and treatments. Already, we have a very robust phase I clinical trials program, having put 161 patients on phase I trials last year.

This means that we are doing more innovative things, not accepting the status quo, which is what you often get in community hospitals.

I get asked all the time: “Don’t only complicated cancers need to get seen in Sylvester?” and I usually say, “Any cancer that you have is complicated.”

There are other things we need to stress:  Sometimes patients spend more time figuring out which flat screen TV they’re going to buy than they do figuring out who should be taking care of them. And so, we tell patients to ask: “How sure are you that you have made the correct diagnosis?”

So many people are misdiagnosed in the US each year, and sometimes people are treated who don’t need to be treated and vice-versa.

For instance, we are working with Moffitt and the University of Florida on pancreas cancer. We’re hoping to look at how many patients in our state are told that with radiation, chemotherapy, and surgery there’s a potential for cure, as opposed to being told that pancreatic cancer is terrible, and you better get your affairs in order.

While the NCI designation, of course, relates to multidisciplinary and collaborative research efforts, we have—given the diversity of our catchment area and community—an important task to educate people in culturally appropriate ways.

 

PG:

Well, there’s a lot happening that actually very good. Having the University of Florida on the path to designation is also wonderful for the state. There’s so much room in there for growth.

SN:

Absolutely. Absolutely.

 

PG:

Since we are talking about Joe Simone’s paper, the word “comprehensive” is in the name of your cancer center. Yet, you don’t—yet—have the NCI-koshered comprehensive designation. Can you change the name? Do you need to?

SN:

The University of Miami’s cancer center started in 1973 shortly after Nixon signed the National Cancer Act. Later, with a naming gift from the Sylvester family, we opened our doors as the Sylvester Comprehensive Cancer Center in 1992. The comprehensive in our name does not refer to an NCI designation. It’s been our name because we have always delivered comprehensive cancer care.

 

PG:

Let’s talk about the Game Changer. That’s such a cool thing. That was one of your center’s great ideas.

SN:

The Game Changer vehicle has been really incredible, already in its impact on our cancer education and early detection programs (The Cancer Letter, April 27, 2018). We’re accruing people for research, and we’re already following some of their health habits.

We’re in the process of delivering HPV vaccines. We have been working with our AIDS group, so you can get PrEP. And we go into communities, like Little Havana, Liberty City, Little Haiti. We are also going into areas to provide education on HIV. As you know, the incidence of HIV in the Miami Dade area is the highest in the nation. So, the vehicle is already having an impact in so many ways.

We’ve just gotten the second Game Changer!

Peter Tunney, the artist, is going to wrap this one also. And this one’s going to focus primarily on Monroe County, which has been hit hard by hurricanes, and also has very poor medical infrastructure.

If you travel to Miami, for business or pleasure, you don’t realize that it’s not that far to get to an extraordinarily rural area. The density of population in Monroe county is very low and access to health care is limited.

The areas that we’re trying to reach have so much socioeconomic gap and disparities. And the Game Changer vehicles are going to help us reach people who otherwise do not access traditional medical systems.

You asked me about the Game Changer vehicle as an idea, and I wanted to shout out the leadership team that we’ve been able to put together at Sylvester. They have been incredible. Our people have worked together in amazing ways. And so, when you say, “That’s a great idea of yours,” yours is the whole team, of course.

 

PG:

Of course.

SN:

It’s remarkable how much work it takes to build the research programs that allow us to even have a competitive application. There were so, so many people who spent so much time for the benefit of the cancer center, and not for their own research.

 

PG:

Can we talk about hurricanes? They have an impact on your mission.

SN:

It’s interesting, because the Sylvester Comprehensive Cancer Center opened its doors in 1992, which is just when Hurricane Andrew hit. I’ve looked through our archives: There are some great articles in the Miami newspaper, because we remained open and provided care right after Hurricane Andrew, which has been the most devastating hurricane here in, I don’t know exactly how many years, maybe 30 or 50 or whatever.

But even following the more recent hurricanes, we’ve been able to provide care for our patients. After Hurricane Irma, in one of our satellites we were open the next day, and we treated 30 patients with chemotherapy who needed it, even though many folks were without electricity.

It’s a unique challenge. We have hurricane preparedness for our laboratories. We have drills for the hospital. And we have a command center.

During Irma, because I live on Miami Beach, in a mandatory evacuation zone, I had to leave my home for a few days. And so, my wife and I slept in the hospital for three nights. There’s food, water, and air conditioning in the hospital. It’s not a bad place to be!

 

PG:

You’re driving now to one of the clinics, even as we speak; right? One of the satellite clinics?

SN:

Yes.

 

PG:

Can you tell me about that?

SN:

We have seven sites where we deliver clinical care. The main site in downtown Miami, and then we have three quite large facilities, one in Coral Gables, one in Plantation, one in Deerfield Beach. And we have three other satellites that are smaller, in Coral Springs, Hollywood, and Kendall.

And this allows us to deliver regional care. We’re all on the same EPIC electronic medical record. And we have patients enrolled on clinical trials in the satellites. Not all the satellites at the moment can have a research pharmacy. But the plan is we’re going to continue our expansion of facilities and services and increase the number of accruals and the sophistication of the trials that are available here. Everybody working in these satellites is a University of Miami employee.

The doctors are all part of our site disease groups, and they teleconference in to meetings and lectures. And many of them spend a day in Miami at the main satellite for education and clinical and other purposes.

Many of the doctors in the satellites are principal investigators on the clinical trials. And it’s important because people don’t want to travel necessarily on the freeways here to get to downtown Miami. And so, we can deliver academic care out in the community, which is always important and a challenging thing to do.

 

PG:

Is there anything we’ve forgotten, anything we need to address?

SN:

Maybe I can talk briefly about the state money for a minute. When Sen. [Rick] Scott [(R-FL)] was the governor, he got us together in his office, the University of Florida, Moffitt, and the University of Miami, and asked us what we needed to become major cancer centers and attain NCI designation so we could have three such facilities in the state.

The next year, the state gave us $10. 5 million to split three ways. So, we each got $3.5 million to bring in somebody from outside the state of Florida, a world-class scientist, and provide them with $500,000 a year for seven years.

We brought Ramin Shiekhattar from the Wistar Institute. He’s one of the leaders of our Cancer Epigenetics Program and a year and a half ago, Ramin won one of the highly prestigious NIH Director’s Pioneer Awards. I believe they give 10 out a year.

Next, the state set up a pool of $60 million to be shared between the three institutions each year for five and now six years. These funds are being used so that all three institutions can attain NCI designation. The directors of these cancer centers get along extremely well, and, in a pretty unique model, we created something called the Florida Academic Cancer Center Alliance.

It exists to promote collaborations across our institutions to conduct important cancer research and bring more federal research dollars to the state.

There are one or two other points I’d like to make: Another person we brought in, Gilberto Lopes, is the head of our Global Oncology Program and the editor of the Journal of Global Oncology for ASCO.

He just gave a plenary talk at 2018 ASCO, showing that immunotherapy is better than chemotherapy for the upfront treatment of certain subsets of lung cancer. His talk was one of four plenary talks we’ve recently given at important national cancer meetings.

I think the other message is just the level at which we’re operating on now. We are demonstrating to our community that we have people who are national leaders, and programs that are among the very best in the country. For this, I must thank the incredible team of researchers who work at Sylvester.

I think that, as we recruit more and more people, this designation is going to help us. I’m very pleased that when we submit NIH grants, the reviewers comment upon the environment in Miami, we now get the high scores for the research environment.

 

PG:

This brings up a problem that held back Sylvester for years, which was the lack of independence of the cancer center, or at least it was perceived to be that. Do you have the independence you need now?

SN:

First of all, I would never have left Sloan Kettering without the authority I needed from the leadership of the University of Miami, the health system and the Miller School of Medicine…

 

PG:

Yeah, that’s a good point.

SN:

I should point out, that I am the head of the cancer center, but I’m also the head of the oncology service line for UHealth health system. This arrangement allows me to align the clinical and the research missions in a way that many cancer center directors cannot.

It’s a real privilege, and I have great leadership and great people working on the service line to make our patient care and patient-related activities superb.

 

PG:

Well, that’s hugely important.

Copyright (c) 2018 The Cancer Letter Inc.

More on NCI Designated Cancer Centers can be found here: https://www.cancer.gov/research/nci-role/cancer-centers

Other articles on NCI Cancer Centers on the Open Access Online Journal include:

Salivary Gland Cancer – Adenoid Cystic Carcinoma: Mutation Patterns: Exome- and Genome-Sequencing @ Memorial Sloan-Kettering Cancer Center

Engineered Bacteria used as Trojan Horse for Cancer Immunotherapy

First Cost-Effectiveness Study of Multi-Gene Panel Sequencing in Advanced Non-Small Cell Lung Cancer Shows Moderate Cost-Effectiveness, Exposes Crucial Practice Gap

 

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An Intelligent DNA Nanorobot to Fight Cancer by Targeting HER2 Expression

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

HER2 is an important prognostic biomarker for 20–30% of breast cancers, which is the most common cancer in women. Overexpression of the HER2 receptor stimulates breast cells to proliferate and differentiate uncontrollably, thereby enhancing the malignancy of breast cancer and resulting in a poor prognosis for affected individuals. Current therapies to suppress the overexpression of HER2 in breast cancer mainly involve treatment with HER2-specific monoclonal antibodies. However, these monoclonal anti-HER2 antibodies have severe side effects in clinical trials, such as diarrhea, abnormal liver function, and drug resistance. Removing HER2 from the plasma membrane or inhibiting the gene expression of HER2 is a promising alternative that could limit the malignancy of HER2-positive cancer cells.

 

DNA origami is an emerging field of DNA-based nanotechnology and intelligent DNA nanorobots show great promise in working as a drug delivery system in healthcare. Different DNA-based nanorobots have been developed as affordable and facile therapeutic drugs. In particular, many studies reported that a tetrahedral framework nucleic acid (tFNA) could serve as a promising DNA nanocarrier for many antitumor drugs, owing to its high biocompatibility and biosecurity. For example, tFNA was reported to effectively deliver paclitaxel or doxorubicin to cancer cells for reversing drug resistance, small interfering RNAs (siRNAs) have been modified into tFNA for targeted drug delivery. Moreover, the production and storage of tFNA are not complicated, and they can be quickly degraded in lysosomes by cells. Since both free HApt and tFNA can be diverted into lysosomes, so,  combining the HApt and tFNA as a novel DNA nanorobot (namely, HApt-tFNA) can be an effective strategy to improve its delivery and therapeutic efficacy in treating HER2-positive breast cancer.

 

Researchers reported that a DNA framework-based intelligent DNA nanorobot for selective lysosomal degradation of tumor-specific proteins on cancer cells. An anti-HER2 aptamer (HApt) was site-specifically anchored on a tetrahedral framework nucleic acid (tFNA). This DNA nanorobot (HApt-tFNA) could target HER2-positive breast cancer cells and specifically induce the lysosomal degradation of the membrane protein HER2. An injection of the DNA nanorobot into a mouse model revealed that the presence of tFNA enhanced the stability and prolonged the blood circulation time of HApt, and HApt-tFNA could therefore drive HER2 into lysosomal degradation with a higher efficiency. The formation of the HER2-HApt-tFNA complexes resulted in the HER2-mediated endocytosis and digestion in lysosomes, which effectively reduced the amount of HER2 on the cell surfaces. An increased HER2 digestion through HApt-tFNA further induced cell apoptosis and arrested cell growth. Hence, this novel DNA nanorobot sheds new light on targeted protein degradation for precision breast cancer therapy.

 

It was previously reported that tFNA was degraded by lysosomes and could enhance cell autophagy. Results indicated that free Cy5-HApt and Cy5-HApt-tFNA could enter the lysosomes; thus, tFNA can be regarded as an efficient nanocarrier to transmit HApt into the target organelle. The DNA nanorobot composed of HApt and tFNA showed a higher stability and a more effective performance than free HApt against HER2-positive breast cancer cells. The PI3K/AKT pathway was inhibited when membrane-bound HER2 decreased in SK-BR-3 cells under the action of HApt-tFNA. The research findings suggest that tFNA can enhance the anticancer effects of HApt on SK-BR-3 cells; while HApt-tFNA can bind to HER2 specifically, the compounded HER2-HApt-tFNA complexes can then be transferred and degraded in lysosomes. After these processes, the accumulation of HER2 in the plasma membrane would decrease, which could also influence the downstream PI3K/AKT signaling pathway that is associated with cell growth and death.

 

However, some limitations need to be noted when interpreting the findings: (i) the cytotoxicity of the nanorobot on HER2-positive cancer cells was weak, and the anticancer effects between conventional monoclonal antibodies and HApt-tFNA was not compared; (ii) the differences in delivery efficiency between tFNA and other nanocarriers need to be confirmed; and (iii) the confirmation of anticancer effects of HApt-tFNA on tumors within animals remains challenging. Despite these limitations, the present study provided novel evidence of the biological effects of tFNA when combined with HApt. Although the stability and the anticancer effects of HApt-tFNA may require further improvement before clinical application, this study initiates a promising step toward the development of nanomedicines with novel and intelligent DNA nanorobots for tumor treatment.

 

References:

 

https://pubs.acs.org/doi/10.1021/acs.nanolett.9b01320

 

https://www.ncbi.nlm.nih.gov/pubmed/27939064

 

https://www.ncbi.nlm.nih.gov/pubmed/11694782

 

https://www.ncbi.nlm.nih.gov/pubmed/27082923

 

https://www.ncbi.nlm.nih.gov/pubmed/25365825

 

https://www.ncbi.nlm.nih.gov/pubmed/26840503

 

https://www.ncbi.nlm.nih.gov/pubmed/29802035

 

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Single-cell RNA-seq helps in finding intra-tumoral heterogeneity in pancreatic cancer

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Pancreatic cancer is a significant cause of cancer mortality; therefore, the development of early diagnostic strategies and effective treatment is essential. Improvements in imaging technology, as well as use of biomarkers are changing the way that pancreas cancer is diagnosed and staged. Although progress in treatment for pancreas cancer has been incremental, development of combination therapies involving both chemotherapeutic and biologic agents is ongoing.

 

Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (PDAC) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease.

 

The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology.

 

PDAC is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. In the present study to comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, single-cell RNA-seq (scRNA-seq) was employed to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases. The diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, were identified in PDAC.

 

The researchers found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, it was found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, the findings provided a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/31273297

 

https://www.ncbi.nlm.nih.gov/pubmed/21491194

 

https://www.ncbi.nlm.nih.gov/pubmed/27444064

 

https://www.ncbi.nlm.nih.gov/pubmed/28983043

 

https://www.ncbi.nlm.nih.gov/pubmed/24976721

 

https://www.ncbi.nlm.nih.gov/pubmed/27693023

 

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Lesson 10 on Cancer, Oncogenes, and Aberrant Cell Signal Termination in Disease for #TUBiol3373

Curator: Stephen J. Williams

Please click on the following file to get the Powerpoint Presentation for this lecture

cell signaling 10 lesson_SJW 2019

There is a good reference to read on The Hallmarks of Cancer published first in 2000 and then updated with 2 new hallmarks in 2011 (namely the ability of cancer cells to reprogram their metabolism and 2. the ability of cancer cells to evade the immune system)

a link to the PDF is given here:

hallmarks2000

hallmarks2011

Please also go to other articles on this site which are relevant to this lecture.  You can use the search box in the upper right hand corner of the Home Page or these are few links you might find interesting

Development of Chemoresistance to Targeted Therapies: Alterations of Cell Signaling & the Kinome

Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation: a Compilation of Articles in the Journal http://pharmaceuticalintelligence.com

Feeling the Heat – the Link between Inflammation and Cancer

Lesson 4 Cell Signaling And Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373

Immunotherapy Resistance Rears Its Ugly Head: PD-1 Resistant Metastatic Melanoma and More

Novel Mechanisms of Resistance to Novel Agents

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Gender of a person can affect the kinds of cancer-causing mutations they develop, according to a genomic analysis spanning nearly 2,000 tumours and 28 types of cancer. The results show striking differences in the cancer-causing mutations found in people who are biologically male versus those who are biologically female — not only in the number of mutations lurking in their tumours, but also in the kinds of mutations found there.

 

Liver tumours from women were more likely to carry mutations caused by a faulty system of DNA mending called mismatch repair, for instance. And men with any type of cancer were more likely to exhibit DNA changes thought to be linked to a process that the body uses to repair DNA with two broken strands. These biases could point researchers to key biological differences in how tumours develop and evolve across sexes.

 

The data add to a growing realization that sex is important in cancer, and not only because of lifestyle differences. Lung and liver cancer, for example, are more common in men than in women — even after researchers control for disparities in smoking or alcohol consumption. The source of that bias, however, has remained unclear.

In 2014, the US National Institutes of Health began encouraging researchers to consider sex differences in preclinical research by, for example, including female animals and cell lines from women in their studies. And some studies have since found sex-linked biases in the frequency of mutations in protein-coding genes in certain cancer types, including some brain cancers and advanced melanoma.

 

But the present study is the most comprehensive study of sex differences in tumour genomes so far. It looks at mutations not only in genes that code for proteins, but also in the vast expanses of DNA that have other functions, such as controlling when genes are turned on or off. The study also compares male and female genomes across many different cancers, which can allow researchers to pick up on additional patterns of DNA mutations, in part by increasing the sample sizes.

 

Researchers analysed full genome sequences gathered by the International Cancer Genome Consortium. They looked at differences in the frequency of 174 mutations known to drive cancer, and found that some of these mutations occurred more frequently in men than in women, and vice versa. When they looked more broadly at the loss or duplication of DNA segments in the genome, they found 4,285 sex-biased genes spread across 15 chromosomes.

 

There were also differences found when some mutations seemed to arise during tumour development, suggesting that some cancers follow different evolutionary paths in men and women. Researchers also looked at particular patterns of DNA changes. Such patterns can, in some cases, reflect the source of the mutation. Tobacco smoke, for example, leaves behind a particular signature in the DNA.

 

Taken together, the results highlight the importance of accounting for sex, not only in clinical trials but also in preclinical studies. This could eventually allow researchers to pin down the sources of many of the differences found in this study. Liver cancer is roughly three times as common in men as in women in some populations, and its incidence is increasing in some countries. A better understanding of its aetiology may turn out to be really important for prevention strategies and treatments.

 

References:

 

https://www.nature.com/articles/d41586-019-00562-7?utm_source=Nature+Briefing

 

https://www.nature.com/news/policy-nih-to-balance-sex-in-cell-and-animal-studies-1.15195

 

https://www.ncbi.nlm.nih.gov/pubmed/26296643

 

https://www.biorxiv.org/content/10.1101/507939v1

 

https://www.ncbi.nlm.nih.gov/pubmed/25985759

 

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