Dr. Choudhury on Targeted Therapy in Prostate Cancer

Atish D. Choudhury, MD, PhD, co-director of the Prostate Cancer Center, senior physician, Dana-Farber Cancer Institute, and instructor in medicine, Harvard Medical School, discusses the use of targeted therapy in prostate cancer.

The most prominent targeted therapies are those that target the androgen receptor (AR), says Choudhury. However, there are several promising approaches that target signaling pathways other than the AR pathway, including AKT inhibitors. For example, patients who have lost PTEN seem to be more responsive to downstream inhibition of AKT.

Then, there are PARP inhibitors, which seem to benefit patients with BRCA1/2 mutations. There may also be overlap between ATM and DNA damage response, although this has yet to be fully elucidated, says Choudhury. The initial publication demonstrating a benefit with olaparib (Lynparza) in the metastatic setting seemed to include patients with ATM loss. However, in the TRITON study, patients with ATM mutations did not seem to have a response to PARP inhibitors. Now the theory is that PARP inhibitors are only beneficial in patients with BRCA1/2 alterations.