2012 Program Booklet - MCD Biology - University of Colorado Boulder

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John T. Schiller, PhD Head, Neoplastic Disease Section Deputy Laboratory Chief Laboratory of Cellular Oncology National Cancer Institute, Bethesda, MD. Title: Understanding and Learning from the Success of Human Papillomavirus Prophylactic Vaccines Saturday, October 13 2:00 – 2:45 pm JSCBB Butcher Auditorium Abstract: The development of antimicrobial vaccines is undoubtedly one of the greatest triumphs of biomedical research. Given the extraordinary effectiveness of vaccines against a wide array of bacterial and viral pathogens, the failure to develop effective vaccines against the most common sexually transmitted infections, especially HIV, has been both surprising and frustrating. The only notable exception is the development of prophylactic vaccines against genital human papillomaviruses (HPVs), the primary etiologic agents in an estimated 5% of human cancers, most importantly cervical cancer. In recently concluded clinical trials, the vaccines were safe and very effective at preventing sexually transmitted infection and the neoplastic diseases induced by the HPV types targeted by the vaccines. They are now licensed in many countries worldwide for the prevention of cervical and other HPV-‐associated cancers and various other hyperproliferative diseases. It is therefore interesting to examine why the HPV vaccines have succeeded whereas those targeting other sexually transmitted infections (STIs) have failed. In this seminar, I will briefly review the association of HPVs with human cancer and other neoplastic diseases, describe the composition of the two commercial vaccines and summarize their efficacy in clinical trials and their emerging effectiveness in general vaccination programs. Specific aspects of HPV molecular biology and vaccine composition that likely contribute to their remarkable success will then be discussed. Finally, I will speculate on how the lessons learned from the HPV vaccines might influence the future of vaccine development for other STIs, particularly HIV and herpes simplex.
Jeffrey Settleman, PhD Senior Director, Discovery Oncology Genentech Title: The Many Flavors of Resistance to Anti-‐Cancer Drugs Saturday, October 13 3:15 – 4:00 pm JSCBB Butcher Auditorium Abstract: The recent clinical success experienced with several “rationally-‐targeted” anti-‐cancer drugs, such as the kinase inhibitors imatinib, erlotinib, crizotinib, and vemurafenib, has defined a paradigm shift in cancer therapy. However, despite the sometimes impressive clinical activity associated with these agents, progression during therapy is inevitable due to the acquisition of drug resistance. For many drugs, specific genetic mechanisms of resistance have been elucidated, and pre-‐clinical findings implicate additional non-‐genetic mechanisms. Moreover, accumulating evidence implicates heterogeneity within cancer cell populations in the response to drug treatment, posing an additional challenge to the development of effective cancer therapeutics. While modeling the acute response to various anti-‐cancer agents in drug-‐sensitive tumor cell lines, we consistently observed a small subpopulation of reversibly “drug-‐tolerant” cells. This drug-‐tolerant phenotype, associated with a distinct chromatin state, is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-‐tolerant subpopulation can be selectively ablated by treatment with chromatin-‐modifying agents, potentially yielding a therapeutic opportunity. These findings suggest that cancer cell populations employ an epigenetically-‐regulated dynamic survival strategy in which individual cells transiently assume a reversibly drug-‐tolerant state to protect the population from eradication by potentially lethal exposures. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell survival effectors -‐ most notably, phosphatidylinositol 3-‐kinase and mitogen-‐activated protein kinase. Consequently, increased RTK ligand levels, via autocrine tumor cell production, paracrine contribution by tumor stroma, or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signaling output. Using a panel of kinase-‐“addicted” cancer cell lines, we found that most cells can be “rescued” from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor confers resistance to the BRAF inhibitor vemurafenib in BRAF mutant melanoma cells. These observations highlight the extensive redundancy of RTK-‐transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.
Page 1 and 2: 26 TH MCDB Graduate Student Symposi
Page 3 and 4: Past MCDB Graduate Student Symposia
Page 5 and 6: Keynote Speaker: William Freytag, P
Page 7 and 8: Keynote Speaker: Larry Gold, PhD Ch
Page 9 and 10: William S. Marshall, PhD President
Page 11: JoAnne Flynn, PhD Professor, Depart
Page 15 and 16: William Sullivan, PhD Professor, De
Page 17 and 18: Symposium Location Jennie Smoly Car
Page 19 and 20: 2012 PRESENTING SPONSORS Arts and S

2012 Program Booklet - MCD Biology - University of Colorado Boulder

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