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Post ASCO GU 2018

MedSIR team attended ASCO GU 2018 in San Francisco, where experts discussed emerging targets, diagnostics, therapies in advanced prostate Cancer among other key relevant topics. Several experts discussed the changing field of advanced prostate cancer management on February 8.

Padmanee Sharma, MD, PhD, of The University of Texas MD Anderson Cancer Center, spoke about the difficulties associated with using immunotherapy approaches in prostate cancer, and how some new research may help address those problems. As the approved indications for immune checkpoint therapy expand year after year, that question has become relevant both within a given oncologic setting and across malignancies. More specifically, outstanding questions include what cellular and molecular mechanisms are involved in antitumor effects with immunotherapy, and whether we can identify predictive, prognostic, or pharmacodynamic biomarkers to guide treatment. Ideal combination therapies with immune checkpoint inhibitors and standard-of-care therapies are also under investigation.

The complicated genomic landscape is under study. A better understanding of the molecular landscape of prostate cancer could obviously result in improved management of the malignancy. Kim N. Chi, MD, FRCPC, of the University of British Columbia, in Vancouver, spoke about incorporating genomics into the management of systemic therapy for CRPC.

A lot of effort has been put into genomic profiling of prostate cancer, Dr. Chi said, and this has revealed driver mutations that have clinical relevance. However, biopsies to look for some of those mutations are invasive and not always feasible in metastatic disease. Liquid biopsies, involving analysis of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), offer an alternative that permits serial sampling over a patient’s disease course.

An emergency option is molecular radiotherapy, Joe M. O’Sullivan, MD, of Queen’s University Belfast, in Northern Ireland, spoke about the potential of molecular therapies in bone metastases. “Targeting bone metastases really matters in mCRPC” he said. “Up to 90% of patients with advanced CRPC will have metastases in their bones. In fact, bone metastases are the main cause of death in prostate cancer.”

However, he said, the phenotype of prostate cancer in the bone facilitates both imaging and therapy of these sites. The change to the normal bone environment associated with prostate cancer metastases allows the imaging with technetium-99, conjugated with methylene diphosphonate. One can deliver a radioactive payload to the metastatic site using the same basic principle.

Molecular radiotherapy uses alpha particles, which are relatively massive and very energetic, but can only travel a short distance through tissue. “Alpha particle radiation is a very effective way of delivering high-energy radiation over a short distance”, Dr. O’Sullivan said. Radium-223 is currently being studied in this setting; it has a dual mode of action, targeting both the metastatic prostate cancer cells themselves as well as the osteoblasts and osteoclasts that can promote tumor growth, as described by Dave Levitan on the daily news genitourinary cancers symposium on February 9, 2018.




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