Prostate cancer is a genomically heterogeneous disease. Understanding these genomic differences might be able to guide us to make better treatment decisions. This idea is supported by the results of an extensive prospective study presented by Robert B. Den, MD, at the 2017 Society of Urologic Oncology Annual Meeting.
In this study, Den found that genomic subtypes in the localized disease setting had distinct drug response profiles, suggesting that classifying men’s prostate cancer into subtypes may be useful for treatment decisions, selecting men for appropriate clinical trials, and for providing translatable clinical tools for personalizing postoperative androgen-deprivation therapy (ADT).
In this study that evaluated 15,136 men, the investigators generated patient-specific drug response scores (DRS) from radical prostatectomy tissue. They created a DRS for 89 drugs administered to 954 men across 36 cell lines with known drug treatment outcomes.
Drug sensitivity for the 89 different agents was determined using the NCI-60 panel, which employs 60 different human tumor cell lines to identify and characterize novel compounds with growth inhibition or killing of tumor cell lines.
The researchers classified the tumor tissue into four different subtypes; basal, luminal A, luminal B, and neuroendocrine by using the PAM50 profiling test and small cell gene expression signatures.
The testing classified 43% of samples in the radical prostatectomy cohort as basal, 26% as luminal A, 30% as luminal B, and 2% as neuroendocrine.
They found that
1- Basal tumors were more sensitive to kinase inhibitors, mTOR inhibitors, DNA repair inhibitors, antineoplastic agents, and alkylating chemotherapies. They also found Basal tumors were also predicted to be more sensitive to platinum-based chemotherapies and topoisomerase inhibitors.
2- Luminal A and B subtype tumors were more sensitive to steroid inhibition such as abiraterone, anti-proliferative chemotherapies, and anti-microtubule chemotherapies. Luminal A and B subtypes were also predicted to be more sensitive to taxane-based therapy.
3- Neuroendocrine tumors were most sensitive to antiproliferative agents, such as mitomycin and topotecan.
“While further validation is necessary, we believe that this technology has the potential to improve patient treatment decisions with regard to chemotherapy,” Den and colleagues said in their poster.
This information, although early was generated using a large cohort of samples. We believe that having a conversation with your oncologist about factoring in these findings and your genic subtype as you make treatment decisions is now an appropriate action for you to take.
Joel T. Nowak, MA, MSW wrote this Post. Joel is the CEO/Executive Director of Cancer ABCs. He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.
