Cancer Research and Oncology 2017 Speaker Highlights from This Week’s Conference
The 5th Annual LabRoots Cancer Research & Oncology Virtual Conference is this week. Be sure not to miss viewing all speakers on demand any time. With topics such as Computational Oncology, Data and Bioinformatics, Organ Systems & Oncogenes, Urologic Oncology, KRas-driven cancers, Circulating Tumor Cells, Therapeutics and Anti-cancer Drug Discovery, Traditional vs novel therapeutics, Screening and Imaging, and Personalized diagnostics, this year’s conference is sure to provide attendees with a new level of understanding of advances in cancer research today.
The conference also offers the opportunity to watch all webinars on demand and provides free CME and CE credits to attendees for each webinar viewed. The keynote speakers this week delivered excellent and informative presentations. If you missed them this week, here are some highlights.
Len Neckers, PhD, Senior Investigator at the National Cancer Institute, Center for Cancer Research gave a Keynote Presentation on “Targeting Molecular Chaperones in Cancer: Lessons Learned from HSP90.”
The first small molecule inhibitor of the molecular chaperone Heat Shock Protein 90 (HSP90) was identified more than 20 years ago. Upon determination of the drug binding site and clarification of its mechanism of action, HSP90 was validated as an anti-cancer molecular target, robust preclinical activity was demonstrated, and the first clinical trials of an HSP90 inhibitor in cancer patients were initiated several years later. Since then, additional natural product and synthetic HSP90 inhibitors have been identified and many have been clinically evaluated.
While numerous clinical trials have been performed with HSP90 inhibitors and encouraging data have been obtained, no HSP90 inhibitor has yet received FDA approval. HSP90 inhibition causes upregulation of the cytoprotective heat shock response, a broad transcriptional response to proteotoxic stress regulated by the transcription factor Heat Shock Factor 1 (HSF1). HSF1 also mediates a cancer-specific transcriptional program. Dr. Neckers’ lab has recently showed that HSP90 binding to HSF1 depends on HSP90 conformation and is only readily visualized for the ATP-dependent, N-domain dimerized chaperone, a conformation only rarely sampled by mammalian HSP90.
Further, they found that ATP-competitive, N-domain targeted HSP90 inhibitors disrupt this interaction, resulting in the increased duration of HSF1 occupancy of the hsp70 promoter and suggesting a role for HSP90 in feedback regulation of the proteotoxic stress response. Another consistent property of HSP90 inhibitors to concentrate in tumors and to remain for an extended time period compared to normal tissues has prompted the use of HSP90 inhibitors as intracellular delivery vehicles to direct and concentrate conjugated cytotoxic agents in tumor while sparing normal tissues. This strategy extends the potential clinical utility of HSP90 inhibitors in cancer and a Phase 1 trial of such an HSP90-drug conjugate is underway.
Dr. Neckers joined the NCI in 1981. He became Chief of the Tumor Cell Biology Section, Medicine Branch, in 1988. An early proponent of translational research, Dr. Neckers pioneered development of oligonucleotide-based therapeutic strategies. Recently, Dr. Neckers has been investigating the role of chaperone proteins in signal transduction. He continues to examine the pivotal role of Hsp90 in cancer cell survival, and participates in the ongoing translational development of Hsp90 inhibitors as novel anti-cancer agents.
Keynote Presenter George Perdrizet, MD, PhD, FACS, Professor and Endowed Chair in Hyperbaric Medical Research and Emergency Medicine at the UC San Diego Health System discussed “Tumor Re-oxygenation – Basic and Therapeutic Considerations.”
Dr. Perdrizet discussed the role played by inflammatory hypoxia in biology and treatment of solid tumors, along with the opportunity to enhance all forms of current anti-tumor therapies through tumor re-oxygenation therapy using hyperbaric oxygen.
Dr. Perdrizet holds the Ted and Michele Gurnee Endowed Chair in Hyperbaric Medicine and Professor of Emergency Medicine at UC San Diego. He is board certified in General Surgery and Hyperbaric Medicine and practiced general, transplant, trauma surgery and wound care in Hartford Connecticut for 20 years before recently relocating to Southern California to focus on translational research in hyperbaric medicine. His interests are in understanding the cellular response to stress and how it may be manipulated by HBOT in the setting of acute and chronic tissue hypoxia.
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