ASCO GU 2017: Luminal and basal subtyping of prostate cancer. - Session Highlights
Although the “cell of origin” for prostate cancer (PCa) has long been thought to be luminal, we now have evidence that perhaps a basal cell origin is also involved in certain tumors. The PAM50 gene classification set is a set of known gene sets that have been used in breast cancer to characterize basal vs. luminal expression subtypes. When applying this same classifier to prostate cancer, a remarkably similar expression pattern naturally arises; and there is a clearly distinct basal vs. luminal pattern that becomes apparent. Furthermore, the luminal subtype appears to be comprised of two distinct subtypes (Luminal A and Luminal B.) More granular characterizations of the gene sets in these three subtypes (Basal, Luminal A, Luminal B) demonstrates different biological pathways that are differentially up- or down-regulated.
After following the long-term outcomes of PCa patients that have these various expression profiles, the team has found that Luminal B subtype patients have the worst outcomes in terms of disease-specific and overall mortality, as well as higher rates of metastatic progression.
Dr. Feng highlighted the recently published RTOG 96-01 study published in NEJM showing a clinical benefit to RT + ADT vs. RT alone in patients with recurrent prostate cancer. The pertinent question here is: Can we use biomarkers to identify those that actually benefit from ADT vs. those who would be cured with RT alone or those in whom no therapy would benefit anyways?
New trials are underway to answer that question by randomizing patients with recurrent PCa and known molecular subtype to RT vs. RT + ADT. Hopefully studies such as this will show us whether molecular subtyping will provide the necessary information needed for appropriate treatment selection for patients with aggressive but potentially curable PCa.
Efforts to bridge the gaps in our knowledge of advanced PCa by utilizing knowledge from other similar cancers (i.e. breast cancer) are key to furthering our full understanding of the disease. The luminal vs. basal subtyping represents an important and clinically useful step in this direction, and may prove to be an important molecular factor to incorporate into more prospective studies.
First author: Felix Feng
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA