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Live Notes from @AACR’s #cbi16 Meeting on Precision Medicine: 3:45PM Big Idea Dr. Hait and Premalignancy

Posted in Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Prevention: Research & Programs, Cancer Screening, Conference Coverage with Social Media, Uncategorized, tagged , , , , , , on January 21, 2016| Leave a Comment »

 Live Notes from @AACR’s #cbi16 Meeting on Precision Medicine: 3:45PM Big Idea Dr. Hait and Premalignancy

Big Idea: Interception: Search for therapies that can tackle pre-malignancies to prevent cancer by Dr. Williams Hait, Global Head Drug Discovery Jansenn

Reporter: Stephen J. Williams, Ph.D.

  • We accumulate diseases over our lifetime
  • Jannsen decided to come up with the term “immorbidity” living longer without fear of disease
  • genetic complexity of cancers increase over time Nature 2012 paper
  • with Gleevec different relapse picture with early than advanced disease (see my post on Gleevec resistance)
  • cancer prevention screens have been important (Pap smears, colonoscopies)
  • MGuS (myeloma precursor) to SMM then full blown disease
  • huge knowledge gap in premalignant myeloma disease and karyotypic changes
  • Jannsen is focusing on disease prevention

 

 

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Live Notes From AACR TownHall on Precision Medicine January 21, 2016 in Philadelphia, PA

Posted in Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Informatics, Cancer Prevention: Research & Programs, Cancer Screening, Conference Coverage with Social Media, Uncategorized, tagged , , , , on January 21, 2016| Leave a Comment »

Live Notes From AACR TownHall on Precision Medicine January 21, 2016 in Philadelphia, PA: Background Information on Speakers

Reporter: Stephen J. Williams, Ph.D.

The Speakers:

Margaret Foti, PhD, MD (hc)

Chief Executive Officer
Margaret Foti, PhD, MD (hc)
​American Association for Cancer Research
Philadelphia, Pennsylvania

Margaret Foti, PhD, MD (hc), is the chief executive officer of the American Association for Cancer Research (AACR), the oldest cancer research organization in the world. Under her visionary leadership, membership has grown from about 3,000 members to 35,000 in 101 countries and the AACR’s portfolio of peer-reviewed scientific journals has increased from one to eight.

Chi Van Dang, MD, PhD

faculty photo

John H. Glick, M.D. Abramson Cancer Center Director’s Professor
Director, Abramson Cancer Center, University of Pennsylvania

 

Selected Publications:

Koppenol WH, Bounds PL, Dang CV: Otto Warburg’s contributions to current concepts of cancer metabolism. Nature Reviews Cancer 11 (5): 325-337,2011.

Dang CV, Hamaker M, Sun P, Le A, Gao P: Therapeutic targeting of cancer cell metabolism Journal of Molecular Medicine 89 (3): 205-212,2011.

Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG, Ferraris DV, Tsukamoto T, Rojas C, Slusher BS, Rabinowitz JD, Dang CV, Riggins GJ: Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1. Cancer Research 70 (22): 8981-8987,2010.

Wang, JB, Erickson, JW, Fuji, R, Ramachandran, S, Gao, P, Dinavahi, R, Wilson, KF, Ambrosio, ALB, Dias, SMG, Dang, CV, Cerione, RA: Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation (vol 18, pg 207, 2010) Cancer Cell 18 (4): 397,2010.

Otto AE, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, Patil SB, Levy S, Ghosh A K, Murga-Zamalloa CA, van Reeuwijk J, Letteboer SJF, Sang L, Giles RH, Liu Q, Coene KLM, Estrada-CuzcanA, Collin RWJ, McLaughlin HM, Held S, Kasanuki JM, Ramaswami G, Conte J, Lopez I, Washburn J, MacDonald J, Hu J, Yamashita Y, Maher ER, Guay-Woodford L, Neumann HPH, Obermüller N, Koenekoop RK, Bergmann C, Bei X, Lewis RA, Katsanis N, Lopes V, Williams DS, Lyons RH, Dang CV, Brito DA, Zhang X, Dias MB, Nürnberg G, Nürnberg P: Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature Genetics 42 (10): 840-50,2010.

Dang CV: Glutaminolysis Supplying carbon or nitrogen or both for cancer cells? Cell Cycle 9 (19): 3884-3886,2010.

Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio ALB, Dias SMG, Dang CV, Cerione RA: Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation. Cancer Cell 18 (3): 207-219,2010.

Koh, CM, Bierberich CJ, Dang CV, Nelson WG, Yegnaubramanian S, De Marzo A: Myc and prostate cancer. Genes & Cancer 1 (6): 617-628,2010.

Fan J, Zeller K, Chen YC, Watkins T, Barnes KC, Becker KG, Dang CV, Cheadle C: Time-Dependent c-Myc Transactomes Mapped by Array-Based Nuclear Run-On Reveal Transcriptional Modules in Human B Cells. Plos One 5 (3): e9691,2010.

Dang CV: p32 (C1QBP) and Cancer Cell Metabolism: Is the Warburg Effect a Lot of Hot Air? Molecular And Cellular Biology 30 (6): 1300-1302,2010.

Nancy E. Davidson, MD

photo

Director, University of Pittsburgh Cancer Institute

Hillman Professor of Oncology

Associate Vice Chancellor for Cancer Research

Distinguished Professor of Medicine

Richard I. Fisher, MD,

President and CEO

Cancer Center Director

Senior Associate Dean, Lewis Katz School of Medicine, Temple University

Robert C. Young, MD, Chair in Cancer Research

Richard Fisher, MD

Stephan A. Grupp, MD, PhD,director of the Cancer Immunotherapy Frontier Program, director of Translational Research for the Center for Childhood Cancer Research at CHOP and medical director of the Stem Cell Laboratory

Stephan A. Grupp, MD, PhD, is director of the Cancer Immunotherapy Frontier Program, director of Translational Research for the Center for Childhood Cancer Research at CHOP and medical director of the Stem Cell Laboratory.

Areas of Expertise: Development of engineered T cell therapies such as CTL019, Novel leukemia therapy, Stem cell transplants, Treatment of high-risk neuroblastoma

Working with our colleagues at the University of Pennsylvania, we have recently opened a phase I clinical trial called CART19. We’re using genetically modified T cells in this trial to treat patients with B cell cancers such as ALL, B cell non-Hodgkin lymphoma (NHL), the adult disease chronic lymphocytic leukemia and other B cell malignancies. T cells have the potential to kill cancer cells, but in patients with cancer, they’re not doing their job. By modifying them we can make the cells behave differently so they’ll attack cancer cells, using an engineered targeting protein called a chimeric antigen receptor (CAR). Initial results show that this could be an effective therapy for patients with B cell cancers. Indeed, our initial results show some of the most powerful activity against cancer of any clinical trial testing engineered cell therapy to date. This has received international attention, and some of this work has been published recently in Science Translational Medicine and the New England Journal of Medicine.

Karen E. Knudsen, PhD,Director of the Sidney Kimmel Cancer Center (SKCC) at Jefferson

kxk016

Expertise & Research Interests

Prostate cancer is the most commonly diagnosed malignancy in the Unites States and the second leading cause of cancer death in men. Early prostate cancers require androgen to survive and proliferate; this dependence is exploited in treatment for disseminated disease. Wherein androgen ablation in the first line of therapeutic intervention. Although these regimens are initially effective, tumors ultimately recur due to reactivation of androgen receptor (AR) signaling, causing treatment failure and patient morbidity.

Despite the importance of understanding androgen action in the prostate, little is understood about the mechanisms underlying androgen dependence, and the means by which the androgen requirement is bypassed in relapsed tumors. My lab is dedicated to delineating the molecular mechanisms that govern these events. We currently have four main projects in the lab:

1. Regulation of AR dependent gene expression and cellular proliferation by cell cycle crosstalk in prostate cancer

2. Impact of SWI/SNF chromatin remodeling factors on AR function and prostate tumorigenesis

3. Impact of cell cycle deregulation on therapeutic efficacy

4. Role of endocrine disrupting compounds in circumventing the androgen requirement

George C. Prendergast, PhD, President and CEO, Lankenau Institute for Medical Research

Photo of George Prendergast

By studying disease modifier genes we seek to develop new principles to treat cancer, diabetes, autoimmune disorders and cardiovascular disease. Currently most biomedical research focuses on understanding disease pathways. We seek to understand general disease modifier pathways that determine disease severity, an understudied area from which many useful drugs such as NSAIDs and statins are based. A major thrust of our present work focuses on modifiers of inflammatory processes which contribute significantly to the severity of many age-associated diseases. In our main project, we have developed a new class of drugs that recruit the immune system to eradicate a broad spectrum of advanced cancers, including breast, lung, skin, and pancreas tumors that are often refractory to chemotherapy. These drugs, called IDO inhibitors, are presently in Phase II clinical trials. In other projects, with our Lankenau colleagues we are developing new agents to treat autoimmune disorders, reduce risks of cardiovascular disease, and ameliorate diabetes.

Scientific Description

Our laboratory is interested primarily in cancer genes, cancer immunology and molecular therapeutics. We use transgenic mouse models and preclinical drug strategies to learn new ways to suppress cancer, focusing on long-term goals of improving strategies for cancer prognosis and treatment.

Localized tumors are often curable if they are detected before progression to invasive status, but many patients diagnosed with cancer already have invasive disease. What factors dictate malignant progression and how might they be therapeutically exploited? Molecular therapeutics that target key oncogene and tumor suppressor pathways show some clinical promise, but they have shown limited efficacy to date. Cancer modifier pathways that influence the immune microenvironment of tumor cells may strongly influence clinical course. Accordingly, new therapies we are developing are based on blocking enzymes that limit the ability of immune cells to destroy cancer cells or drive disease.

RhoB studies derive from our long-standing research on this member of the Ras/Rho superfamily in cancer cell signaling. Recent work in collaboration with Drs. Lisa Laury-Kleintop and Laura Mandik-Nayak at Lankenau has opened exciting new directions in studies of the role of RhoB in autoimmune and cardiovascular disease. A start-up company has been created to fund and advance the preclinical and clinical work needed to explore a provocative new therapy emerging from these novel directions, which in principle may be useful to treat one or more diseases in important areas of medicine.

Bin1 studies originating in cancer cell studies led us to discover that it regulates the immune modulatory enzyme indoleamine 2,3-dioxygenase (IDO). Bin1 modifies inflammation in a variety of settings including cancer. Recently, in preclinical studies we found that its genetic blockade can limit the development of inflammatory bowel disease (colitis). Based on this finding, we are now investigating the use of Bin1 antibodies we have developed to treat this disorder.

IDO is a tryptophan catabolic enzyme that blocks T cell activation in physiological settings such as pregnancy and in many pathophysiological settings like cancer. IDO is very widely activated as a mechanism of immune escape by cancer cells. Genetic studies reveal that IDO is essential for inflammation-driven cancers, not only supporting immune escape but also angiogenesis and metastasis. We pioneered preclinical studies of IDO inhibitory drugs that can arrest tumor growth and enhance chemotherapeutic efficacy. Mechanistic studies of one clinical lead inhibitor, D-1MT (indoximod), will greatly assist ongoing Phase II studies of this drug. Translational studies including on an IDO-related gene called IDO2 discovered at Lankenau are currently a major focus of the laboratory.

 

 

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