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Archive for the ‘Cancer and Current Therapeutics’ Category


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

WASHINGTON (June 27, 2019) — The results of the first economic modeling study to estimate the cost-effectiveness of “multi-gene panel sequencing” (MGPS) as compared to standard-of-care, single-gene tests for patients with advanced non-small cell lung cancer (aNSCLC) show that the MGPS tests are moderately cost-effective but could deliver more value if patients with test results identifying actionable genetic mutations consistently received genetically guided treatments. The results of the study, which was commissioned by the Personalized Medicine Coalition (PMC), underline the need to align clinical practices with an era of personalized medicine in which physicians can use diagnostic tests to identify specific biological markers that inform targeted prevention and treatment plans.

The study, which was published yesterday in JCO Clinical Cancer Informatics, analyzed the clinical and economic value of using MGPS testing to identify patients with tumors that over-express genetic mutations that could be targeted by available therapies designed to inhibit the function of those genes — a mainstay of modern care for aNSCLC patients. Using data provided by Flatiron Health, researchers examined clinical and cost information associated with the care of 5,688 patients with aNSCLC treated between 2011 – 2016, separating them into cohorts who received MGPS tests that assess at least 30 genetic mutations at once and those who received only “single-marker genetic testing” (SMGT) of less than 30 genes.

Compared to SMGT, the MGPS testing strategy, including downstream treatment and monitoring of disease, incurred costs equal to $148,478 for each year of life that it facilitated, a level suggesting that MGPS is moderately cost-effective compared to commonly cited thresholds in the U.S., which range from $50,000 to $200,000 per life year (LY) gained.

The authors of the study point out, however, that physicians only prescribed a targeted therapy to some of the patients whose MGPS test results revealed actionable mutations. MGPS tests can only improve downstream patient outcomes if actionable results are used to put the patient on a targeted treatment regimen that is more effective than the therapy they would otherwise have been prescribed. It is therefore impossible for the cost of an MGPS test to translate into additional LYs if actionable results do not result in the selection of a targeted treatment regimen.

Although MGPS testing revealed actionable mutations in 30.1 percent of the patients in the study cohort, only 21.4 percent of patients who underwent MGPS testing received a targeted treatment.

The study’s authors calculated that if all MGPS-tested patients with actionable mutations had received a targeted therapy, MGPS testing would deliver measurably better value ($110,000 per LY gained).

“This research underlines the importance of ensuring that clinical practices keep pace with scientific progress in personalized medicine so that we can maximize the benefits of diagnostic tests that can improve patient care and make the health system more efficient by ensuring that safe and effective targeted therapies are prescribed to those patients who will benefit,” said PMC President Edward Abrahams.

The study’s authors include Dr. Lotte Steuten, Vice President and Head of Consulting, The Office of Health Economics, London, U.K., and Affiliate Associate Faculty Member, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center; Dr. Bernardo Goulart, Associate Faculty Member, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center; Dr. Neal Meropol, Vice President, Research Oncology, Flatiron Health; Dr. Daryl Pritchard, Senior Vice President, Science Policy, Personalized Medicine Coalition; and Dr. Scott Ramsey, Director, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center.

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About the Personalized Medicine Coalition:

The Personalized Medicine Coalition, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system. For more information, please visit www.personalizedmedicinecoalition.org.

SOURCE

From: Personalized Medicine Coalition <pmc@personalizedmedicinecoalition.org>

Reply-To: “Christopher Wells (PMC)” <cwells@personalizedmedicinecoalition.org>

Date: Thursday, June 27, 2019 at 9:32 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: First Cost-Effectiveness Study of MGPS in aNSCLC Shows Moderate Cost-Effectiveness, Exposes Crucial Practice Gap

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Can Elephants Help Fight Cancer?

Reporter: Gail S. Thornton, M.A.

 

 

This paragraph is excerpted from the American Technion Society Facebook page.

Professor Avi Schroeder and Dr. Josh Schiffman of the The University of Utah are working with elephants at Utah’s Hogle Zoo on a possible new tool to fight against lung, bone, breast, and other cancers. Dr. Schiffman found that p53, a cancer-suppressing protein, is far more prevalent in elephants, which rarely develop cancer. Prof. Schroeder is now working to manufacture the protein in nanoparticles to begin preclinical testing.


This article is excerpted from The Salt Lake Tribune, May 2, 2019.

Earth’s biggest, smallest, oddest life forms are getting new attention from scientists. A Utah author explores what they’re learning.

Published: May 2, 2019

Researchers have long ignored superlative life forms — the biggest, the tiniest, ones that can survive extremes — as outliers, Utah author Matthew D. LaPlante says.

But they’re now realizing the value of studying nature’s “oddballs,” he adds, which are helping scientists discover how to better fight disease and aging, understand the history of life on this planet and how we might reach others.

LaPlante’s new book, “Superlative: The Biology of Extremes” was released this week. On Friday at 7 p.m., the associate professor of journalistic writing at Utah State University will read from “Superlative” and talk about his work at The King’s English Bookshop, 1511 S. 1500 East, Salt Lake City. The event is free and open to the public.

The co-writer of several books on the intersection of scientific discovery and society, LaPlante now is working with Harvard geneticist David Sinclair on a book about human longevity. “Superlative” from BenBella Books is the first solo book by LaPlante, a former reporter for The Salt Lake Tribune.

As he surveys unusual life around the earth, there are stops in Utah — from Pando, the aspen clone in Sevier County believed to be the single most massive living organism known on Earth, to pop-up appearances by researchers at the University of Utah and elephants at Hogle Zoo in Salt Lake City.

Vast sequences of the genetic coding that humans share with elephants still perform similar functions in each species, LaPlante explains. And long after the two diverged, both developed the same genetic solution for the oxygen needs of a larger brain.

So there’s reason to believe that responses elephants have evolved — such as rarely developing cancer — might be spurred in humans.

The potential within a genome for such new traits to develop is at the heart of comparative genomics — and at the work of Utah pediatric oncologist Josh Schiffman.

This excerpt from “Superlative” explains how Schiffman began working with Hogle Zoo’s African elephants — the largest living land mammals — to fight cancer.

It all started in the summer of 2012, when [pediatric oncologist Josh] Schiffman’s beloved dog, Rhody, passed away [due] to histiocytosis, a condition that attacks the cells of skin and connective tissue. “It was the only time my wife has ever seen me cry,” he told me. “Rhody was like our first child.”

Schiffman had heard dogs like his had an elevated risk of cancer, but it wasn’t until after Rhody’s death that he learned just how elevated it was. Bernese mountain dogs who live to the age of ten have a 50 percent risk of dying from cancer.

“Suddenly it dawned on me there was this whole other world, this young field of comparative oncology,” he said, “and I was pulled into the idea of being a pioneer and maybe a leader to help move things along.”

Schiffman had long been intrigued by the fact that size doesn’t appear to correlate to cancer rates — a phenomenon known as “Peto’s Paradox,” named for Oxford University epidemiologist Richard Peto. But when Schiffman took his children on an outing to Utah’s Hogle Zoo — the same place I sometimes go to have lunch with my elephant friend, Zuri — everything came together.

A keeper named Eric Peterson had just finished giving a talk to a crowd of visitors, mentioning in passing that the zoo’s elephants have been trained to allow the veterinary staff to take small samples of blood from a vein behind their ears. As the crowd dispersed, an angular, excited man approached him.

“I’ve got a strange question,” Schiffman said.

“We’ve heard them all,” Peterson replied.

“OK then — how do I get me some of that elephant blood?” Schiffman asked.

Peterson contemplated calling security. Instead, after a bit of explanation from Schiffman, the zookeeper told the inquisitive doctor he’d look into it. Two and a half months later, the zoo’s institutional review board gave its blessing to Schiffman’s request.

Things moved fast after that.

(Steve Griffin | Tribune file photo) Lab specialists Lauren Donovan Cristhian Toruno, Lisa Abegglen and researcher Joshua Schiffman, from left, are testing the effects of elephant gene p53 (EP53) in human cancer cells at the Huntsman Cancer Institute.
(Steve Griffin | Tribune file photo) Lab specialists Lauren Donovan Cristhian Toruno, Lisa Abegglen and researcher Joshua Schiffman, from left, are testing the effects of elephant gene p53 (EP53) in human cancer cells at the Huntsman Cancer Institute.

Cancer develops in part because cells divide. During each division the cells must make a copy of their DNA, and once in a while, for various reasons, those copies include a mistake. The more cells divide, the greater the odds of an error, and the more prone an error is to be duplicated again and again.

And elephant cells? Those things are dividing like crazy. Based on the number of cell divisions elephants need to get from Zuri’s size when we met to the size she is now, in just a few short years, it stands to reason they should get lots of cancer. Yet they almost never do.

“Going from 300 pounds as a calf to more than 10,000 pounds, gaining three-plus pounds a day, they’re growing so quickly, so big and so fast — baby elephants really shouldn’t make it to adulthood,” Schiffman said. “They should have 100 times the cancer. Just by chance alone, elephants should be dropping dead all over the place.” Indeed, he said, they should probably die of cancer before they’re even old enough to reproduce. “They should be extinct!”

Already, comparative oncologists suspected the exceptionally low rate of cancer in elephants had something to do with p53, a gene whose human analog is a known cancer suppressor. Most humans have one copy — two alleles — of the gene. Those with an inherited condition known as Li–Fraumeni syndrome, however, have just one allele — and a nearly 100 percent chance of getting cancer. The logical conclusion is more p53 alleles mean a better chance of staving off cancer. And elephants, it turns out, have twenty of them.

The big find that came from Schiffman’s exploration of the elephant blood he got at the zoo, though, was not just that there were more of these genes in elephants, but that the genes behaved a little bit differently, too.

In humans, the gene’s first approach for suppressing tumor growth is to try to repair faulty cells — the sort that cause cancer. So, at first, Schiffman’s team assumed having more p53 genes meant elephants had bigger repair crews. With the goal of watching those crews in action, the researchers exposed the elephant cells to radiation, causing DNA damage. But they noticed that, instead of trying to fix what was broken, the elephant cells seemed to grow something of a conscience.

To understand this, it’s helpful to think about how you’d respond in a zombie apocalypse. Of course you’d fight long and hard to keep from being infected, right? But if a zombie was about to chomp down on your arm, and there was nothing you could do to stop it, and if you had but one bullet remaining in your gun —and a few moments to consider what you might do to your fellow humans as a part of the legion of the undead — what would you do?

That’s what elephant cells do, too. Under the directive of p53, mutated cells don’t put up a fight. Upon recognizing the inevitability of malignant mutation, they take their own lives in a process known as apoptosis.

And they don’t just do this for one kind of cancer. The p53 gene apparently programs cells to do this in response to all kinds of malignantly mutated cells in elephants—a finding that flies in the face of the conventional assumption that there is no one singular cure for the complex group of disorders we call cancer.

When I first met Schiffman in 2016, he was brimming with excitement about the potential elephants have to help us understand cancer. He was also very cautious not to suggest he was anywhere near a cure, nor that he ever would be.

Just a few years later, though, Schiffman was speaking openly about his intention to rid the world of cancer. And, to that end, what’s happening in his lab is encouraging, to say the least.

He and his team have been injecting cancer cells with a synthetic version of a p53 protein modeled on the DNA he’s drawn from Zuri and other elephants from around the world. Viewed on time-lapse video, the results are unmistakable and amazing.

Breast cancer. Gone.

bone cancer. Gone.

Lung cancer. Gone.

One by one, each type of cancer cell falls victim to zombie-cell hara-kiri, shriveling and then exploding, and leaving nothing behind to mutate. Schiffman is now working with Avi Schroeder, an expert in nanomedical delivery systems at Technion-Israel Institute of Technology, to create tiny delivery vehicles to take the synthetic elephant protein into mammalian tumors.

If this was all the benefit we ever derived from studying elephants, it would be plenty.

But it’s not. Not at all.

Source:

https://www.sltrib.com/artsliving/2019/05/02/earths-biggest-smallest/?fbclid=IwAR09iwADrhUKkuoXDRMBHFIMstUESU3OBXxKeN0dTKwxapTUASWsv1T_kZI

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eProceedings for BIO 2019 International Convention, June 3-6, 2019 Philadelphia Convention Center; Philadelphia PA, Real Time Coverage by Stephen J. Williams, PhD @StephenJWillia2

 

CONFERENCE OVERVIEW

Real Time Coverage of BIO 2019 International Convention, June 3-6, 2019 Philadelphia Convention Center; Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/05/31/real-time-coverage-of-bio-international-convention-june-3-6-2019-philadelphia-convention-center-philadelphia-pa/

 

LECTURES & PANELS

Real Time Coverage @BIOConvention #BIO2019: Machine Learning and Artificial Intelligence: Realizing Precision Medicine One Patient at a Time, 6/5/2019, Philadelphia PA

Reporter: Stephen J Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/05/real-time-coverage-bioconvention-bio2019-machine-learning-and-artificial-intelligence-realizing-precision-medicine-one-patient-at-a-time/

 

Real Time Coverage @BIOConvention #BIO2019: Genome Editing and Regulatory Harmonization: Progress and Challenges, 6/5/2019. Philadelphia PA

Reporter: Stephen J Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/05/real-time-coverage-bioconvention-bio2019-genome-editing-and-regulatory-harmonization-progress-and-challenges/

 

Real Time Coverage @BIOConvention #BIO2019: Precision Medicine Beyond Oncology June 5, 2019, Philadelphia PA

Reporter: Stephen J Williams PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/05/real-time-coverage-bioconvention-bio2019-precision-medicine-beyond-oncology-june-5-philadelphia-pa/

 

Real Time @BIOConvention #BIO2019:#Bitcoin Your Data! From Trusted Pharma Silos to Trustless Community-Owned Blockchain-Based Precision Medicine Data Trials, 6/5/2019, Philadelphia PA

Reporter: Stephen J Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/05/real-time-bioconvention-bio2019bitcoin-your-data-from-trusted-pharma-silos-to-trustless-community-owned-blockchain-based-precision-medicine-data-trials/

 

Real Time Coverage @BIOConvention #BIO2019: Keynote Address Jamie Dimon CEO @jpmorgan June 5, 2019, Philadelphia, PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/05/real-time-coverage-bioconvention-bio2019-keynote-address-jamie-dimon-ceo-jpmorgan-june-5-philadelphia/

 

Real Time Coverage @BIOConvention #BIO2019: Chat with @FDA Commissioner, & Challenges in Biotech & Gene Therapy June 4, 2019, Philadelphia, PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/04/real-time-coverage-bioconvention-bio2019-chat-with-fda-commissioner-challenges-in-biotech-gene-therapy-june-4-philadelphia/

 

Falling in Love with Science: Championing Science for Everyone, Everywhere June 4 2019, Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/04/real-time-coverage-bioconvention-bio2019-falling-in-love-with-science-championing-science-for-everyone-everywhere/

 

Real Time Coverage @BIOConvention #BIO2019: June 4 Morning Sessions; Global Biotech Investment & Public-Private Partnerships, 6/4/2019, Philadelphia PA

Reporter: Stephen J Williams PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/04/real-time-coverage-bioconvention-bio2019-june-4-morning-sessions-global-biotech-investment-public-private-partnerships/

 

Real Time Coverage @BIOConvention #BIO2019: Understanding the Voices of Patients: Unique Perspectives on Healthcare; June 4, 2019, 11:00 AM, Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/04/real-time-coverage-bioconvention-bio2019-understanding-the-voices-of-patients-unique-perspectives-on-healthcare-june-4/

 

Real Time Coverage @BIOConvention #BIO2019: Keynote: Siddhartha Mukherjee, Oncologist and Pulitzer Author; June 4 2019, 9AM, Philadelphia PA

Reporter: Stephen J. Williams, PhD. @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/04/real-time-coverage-bioconvention-bio2019-keynote-siddhartha-mukherjee-oncologist-and-pulitzer-author-june-4-9am-philadelphia-pa/

 

Real Time Coverage @BIOConvention #BIO2019:  Issues of Risk and Reproduceability in Translational and Academic Collaboration; 2:30-4:00 June 3, 2019, Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/03/real-time-coverage-bioconvention-bio2019-issues-of-risk-and-reproduceability-in-translational-and-academic-collaboration-230-400-june-3-philadelphia-pareal-time-coverage-bioconvention-bi/

 

Real Time Coverage @BIOConvention #BIO2019: What’s Next: The Landscape of Innovation in 2019 and Beyond. 3-4 PM June 3, 2019, Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/03/real-time-coverage-bioconvention-bio2019-whats-next-the-landscape-of-innovation-in-2019-and-beyond-3-4-pm-june-3-philadelphia-pa/

 

Real Time Coverage @BIOConvention #BIO2019: After Trump’s Drug Pricing Blueprint: What Happens Next? A View from Washington; June 3, 2019 1:00 PM, Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/03/real-time-coverage-bioconvention-bio2019-after-trumps-drug-pricing-blueprint-what-happens-next-a-view-from-washington-june-3-2019-100-pm-philadelphia-pa/

 

Real Time Coverage @BIOConvention #BIO2019: International Cancer Clusters Showcase June 3, 2019, Philadelphia PA

Reporter: Stephen J. Williams PhD @StephenJWillia2

https://pharmaceuticalintelligence.com/2019/06/03/real-time-coverage-bioconvention-bio2019-international-cancer-clusters-showcase-june-3-philadelphia-pa/

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Real Time Coverage @BIOConvention #BIO2019: Keynote: Siddhartha Mukherjee, Oncologist and Pulitzer Author; June 4 9AM Philadelphia PA

Reporter: Stephen J. Williams, PhD. @StephenJWillia2

 

Hematologist and oncologist Siddhartha Mukherjee was born in New Delhi, India. He holds a BS in biology from Stanford University, a DPhil in immunology from Oxford University (where he was a Rhodes Scholar), and an MD from Harvard Medical School. He completed his internal medicine residency and an oncology fellowship at Massachusetts General Hospital. Dr. Murkherjee is an assistant professor of medicine at Columbia University Medical Center. He lives in Manhattan with his wife, artist Sarah Sze, and their two daughters. His Pulitzer Prize-winning book, The Emperor of All Maladies: A Biography of Cancer, tells the story of cancer from its first description in an ancient Egyptian scroll to the gleaming laboratories of modern research institutions. A three-part documentary series based on the book, directed by Barak Goodman and executive produced by Ken Burns, debuts on PBS stations March 30 and continues on March 31 and April 1. The film interweaves a sweeping historical narrative with intimate stories about contemporary patients and an investigation into the latest scientific breakthroughs. He has also written the award winning book “The Gene: An Intimate History” and is Founder of Vor Biopharma, who had just published on their CD33 engineered hematopoetic stem cells as an immunooncology therapy VOR33.

Hon. James C. Greenwood- former Congressional representative and Founder CEO of BIO: moderator

Greenwood: Never have the threats from DC to innovation in the biotech field been so great.  Focused on some great recent innovations and successes in gene therapy.  Although the cost high, father of two LMR retinopathy patients said if his sons had to go through a lifetime of constant care it would cost much more than the gene therapy from Spark cost.  Politicians need to realize that medicines that completely cure diseases are worth much more.  They should meet in the middle with respect to developing a new payer model that will not hurt innovation.

Dr. Mukherjee:  He go into oncology from a virology PhD because he liked to understand the human aspect

of disease.  As an oncologist he gets to interact more closely with patients.  The oncology horizon is always changing.  He likened his view of oncology and cancer as a pyramid with prevention the base, then early detection then therapy at top.

We haven’t found preventable human carcinogens, none that is highly proven causal

This will be the next challenge for cancer researchers, to figure out why we can’t identify these preventable carcinogens.

 

 

 

 

Please follow on Twitter using these @ handles and # hashtags

@Handles

@DrSidMukherjee

@pharma_BI

@AVIVA1950

@BIOConvention

# Hashtags

#BIO2019 (official meeting hashtag)

 

Other Articles on this Open Access Journal on Interviews with Scientific Leaders Include:

Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders at https://www.amazon.com/dp/B078313281 – electronic Table of Contents

Jennifer Doudna and NPR science correspondent Joe Palca, several interviews

Practicing Oncology: Medscape Editor-in-Chief Eric J. Topol, MD interviews Siddhartha Mukherjee, MD, PhD

Eric Topol interviews Al Gore on Genomics and Privacy

Dr. Mercola Interviews Dr. Saul About Beta-Blockers

Volume Two: Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders

 

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Real Time Coverage @BIOConvention #BIO2019: International Cancer Clusters Showcase June 3, Philadelphia PA

Reporter: Stephen J. Williams PhD @StephenJWillia2

 

Larry Blandford PharmD from Precision Medicine Group gave introduction about development of precision oncology medicine.  Talked about value and value determination for partnerships.

Company Pitches:

Kernal Biologics: Preclinical immunotherapy company developing mRNA therapeutics.  Their therapy only have activity in p53 deficient cells (messenger 2.0).  They identified, by screening, multiple mRNAs that have oncoselectivity; ONC-333 is their lead mRNA active in AML and NSCLC.  Looking for 5.5M seed $

Vaccibody AS: Vaccine technology from Oslo University to target antigen to antigen presenting cells.  They are targeting the myocytes and dimerize the antigen to MHC.  Targeting melanoma, certain cervical cancers, and hemotologic cancers.  Technology based on identified neoantigens obtained from tumor biopsy.Three vaccines: VB10.neo  VB10.16 against HPV cervical

Chimeric Therapeutics: developing CART to solid malignancies against CLEC14 (tumor endothelial marker), may make tumor susceptible to hypoxia.  Targeting pancreatic cancer, prelim results in mice , efficacy of 15%, working on 3rd generation CART

Memo Therapeutics: Antibody therapeutics; based on Dropzylla single B cell sorting and subsequent screening for mAb.  Targeting checkpoint inhibitors on solid tumors;  have a new target other than PD1; target undisclosed on NK cells and T cells; Early stage have academic partners; seeking 20Million Swiss Francs

Takeda Oncology: Chris Hurff Senior Director Business Development; they depend on partnerships as they feel internal RD is less effective.  They are diversifying their portfolio from small molecules. They have over 200 partnerships (132 in Boston). They are focusing on heme, lung, and Immunooncology. Partnering model: CEI (center external innovation) deals with both academic and small biotechs.  They have numerous partners including Shatto and MD Anderson.

 

 

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

 

RNA plays various roles in determining how the information in our genes drives cell behavior. One of its roles is to carry information encoded by our genes from the cell nucleus to the rest of the cell where it can be acted on by other cell components. Rresearchers have now defined how RNA also participates in transmitting information outside cells, known as extracellular RNA or exRNA. This new role of RNA in cell-to-cell communication has led to new discoveries of potential disease biomarkers and therapeutic targets. Cells using RNA to talk to each other is a significant shift in the general thought process about RNA biology.

 

Researchers explored basic exRNA biology, including how exRNA molecules and their transport packages (or carriers) were made, how they were expelled by producer cells and taken up by target cells, and what the exRNA molecules did when they got to their destination. They encountered surprising complexity both in the types of carriers that transport exRNA molecules between cells and in the different types of exRNA molecules associated with the carriers. The researchers had to be exceptionally creative in developing molecular and data-centric tools to begin making sense of the complexity, and found that the type of carrier affected how exRNA messages were sent and received.

 

As couriers of information between cells, exRNA molecules and their carriers give researchers an opportunity to intercept exRNA messages to see if they are associated with disease. If scientists could change or engineer designer exRNA messages, it may be a new way to treat disease. The researchers identified potential exRNA biomarkers for nearly 30 diseases including cardiovascular disease, diseases of the brain and central nervous system, pregnancy complications, glaucoma, diabetes, autoimmune diseases and multiple types of cancer.

 

As for example some researchers found that exRNA in urine showed promise as a biomarker of muscular dystrophy where current studies rely on markers obtained through painful muscle biopsies. Some other researchers laid the groundwork for exRNA as therapeutics with preliminary studies demonstrating how researchers might load exRNA molecules into suitable carriers and target carriers to intended recipient cells, and determining whether engineered carriers could have adverse side effects. Scientists engineered carriers with designer RNA messages to target lab-grown breast cancer cells displaying a certain protein on their surface. In an animal model of breast cancer with the cell surface protein, the researchers showed a reduction in tumor growth after engineered carriers deposited their RNA cargo.

 

Other than the above research work the scientists also created a catalog of exRNA molecules found in human biofluids like plasma, saliva and urine. They analyzed over 50,000 samples from over 2000 donors, generating exRNA profiles for 13 biofluids. This included over 1000 exRNA profiles from healthy volunteers. The researchers found that exRNA profiles varied greatly among healthy individuals depending on characteristics like age and environmental factors like exercise. This means that exRNA profiles can give important and detailed information about health and disease, but careful comparisons need to be made with exRNA data generated from people with similar characteristics.

 

Next the researchers will develop tools to efficiently and reproducibly isolate, identify and analyze different carrier types and their exRNA cargos and allow analysis of one carrier and its cargo at a time. These tools will be shared with the research community to fill gaps in knowledge generated till now and to continue to move this field forward.

 

References:

 

https://www.nih.gov/news-events/news-releases/scientists-explore-new-roles-rna

 

https://www.cell.com/consortium/exRNA

 

https://www.sciencedaily.com/releases/2016/06/160606120230.htm

 

https://www.pasteur.fr/en/multiple-roles-rnas

 

https://www.nature.com/scitable/topicpage/rna-functions-352

 

https://www.umassmed.edu/rti/biology/role-of-rna-in-biology/

 

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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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