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GU Cancers 2018 | Targeting plasticity pathways for novel therapy in prostate cancer

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Andrew Armstrong

From the 2018 Genitourinary Cancers Symposium, held in San Francisco, CA, Andrew Armstrong, MD, from Duke University, Durham, NC, highlights the need for novel therapies targeting plasticity pathways in particular, in order to treat bone metastases in patients with prostate cancer. Dr Armstrong also outlines potential predictive biomarkers, including DNA defects in PARP inhibitors and androgen receptor defects.

Transcript (edited for clarity)

Well right now we need some drug development efforts that focus on plasticity pathways. This has really been an unmet need and very difficult to target, as many normal processes in the body reactivate some of these stem-like processes, so plasticity itself is a actionable target, it is something that drug development should be focused on to prevent bone metastasis.
There is certainly anti-bone resorptive therapies such as dinosinab, zoledronic acid and radium itself, but those drugs are not sufficient to eradicate bone metastasis themselves or to prevent bone metastases...

Well right now we need some drug development efforts that focus on plasticity pathways. This has really been an unmet need and very difficult to target, as many normal processes in the body reactivate some of these stem-like processes, so plasticity itself is a actionable target, it is something that drug development should be focused on to prevent bone metastasis.
There is certainly anti-bone resorptive therapies such as dinosinab, zoledronic acid and radium itself, but those drugs are not sufficient to eradicate bone metastasis themselves or to prevent bone metastases. So more development needs to be done to target those pathways directly.
Right now in clinical practice, we use standard clinical biomarkers like PSA levels, alkaline phosphatase, for example radium has a greater effect on alkaline phosphatase, and not a great effect on PSA. Well for androgen receptor inhibitor therapy, both of these biomarkers can decline, and when you see a drop in those biomarkers, patients live longer so that can be very reassuring.
Some of the emerging biomarkers are more predictive biomarkers such as DNA repair defects for PARP inhibitors androgen receptor mutations or splice variants that can predict whether these drugs like abiraterone or enzalutamide are effective. Immune therapies only work in a subset of men, so identifying predictive biomarkers is really quite an emerging area of work.
We had a poster on Thursday that demonstrated that some prostate cancer circulating tumor cells express immune checkpoints on their surface, it may identify a path forward for a predictive biomarkers for immune therapies and prostate cancer.

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