Multi-omic Analysis Guides the Decisions of Brian McCloskey (Rana McKay, MD, and BostonGene)

May 22, 2024 - Cancer Patient Lab Meeting #98
Discussion forum: community.cancerpatientlab.org

“For the next 4 days, Dr. McKay completely quarterbacked my care across the emergency department, the urology team, the radiation oncology team, her team, and orthopedic surgery.” – Brian McCloskey

“First, we noticed that a lot of tumor cells demonstrate expression of Synaptophysin in the metastatic sample, nearly 38%, and only 3% expression in the primary sample. We then reviewed H&E slides and images and revealed that in the metastatic sample, we also can find areas with neuroendocrine-like features.” – Kirill Kryukov, BostonGene

“The salient thing that I pulled from this report is the striking angiogenesis signature. There are multiple different VEGF pathway genes that are dysregulated. What's important to pull is that there are multiple different targets here, as opposed to just one that could all be targeted with a drug. When I see that, that's a very nice thing as a clinician to say, ‘Hey, this is not just one thing out of a sea of many; there are multiple targets in this pathway… This pathway seems to be off, and that may present a greater vulnerability for the tumor.’
“That's what precision medicine can do. It can help try to identify a specific vulnerability that we can take advantage of with drugs that we otherwise would not be able to.” – Rana McKay, MD, UCSD Health

Meeting Summary
Advanced prostate cancer patients want to know what their next treatment option should be if their existing treatment regimen fails. But that’s a moving target as new treatments are approved, clinical trials of new treatments start, and experience is gained in old and new treatments. It is important to occasionally scan the range of newly approved treatments and research on treatments currently in clinical trials. For example, a number of new drug combinations and sequencing of systemic therapies in metastatic castrate-resistant prostate cancer can hit the cancer harder and earlier.

Dr. Rana McKay is uniquely qualified to talk about the latest personalized approaches to treating men with prostate cancer. She leads a multi-disciplinary prostate cancer clinic at UC San Diego Health focused on delivering advanced cancer care. Her research interests include the design and implementation of clinical trials, including novel biomarkers and therapeutic outcomes for patients with genitourinary malignancies. She is interested in understanding mechanisms of response and resistance to specific cancer therapies. Before joining UC San Diego Health, Dr. McKay was a medical oncologist at the Dana-Farber/Brigham and Women's Cancer Center in Boston and an assistant professor at Harvard Medical School.

Kirill Kryukov presented BostonGene’s analysis of Brian’s cancer, demonstrating the power of transcriptomic (RNA) analysis in identifying key biomarkers. Dr. McKay discussed her interpretation of the test results and considerations of various therapeutic approaches, illustrating the issues and art and science of treatment navigation.

Dr. McKay reviewed the journey of Cancer Patient Lab co-founder Brian McCloskey.

● Advanced prostate cancer, diagnosed in 2016.
● Has had many tests over the years and has been through multiple lines of treatments including a radical prostatectomy, salvage radiation, six lines of systemic therapy, and two additional surgeries to remove metastatic lesions.
● Constriction of his right ureter (the tube that transports urine from the kidneys to the bladder) leading to kidney hydronephrosis (kidney swelling that happens when urine can't drain from a kidney and builds up in the kidney) and kidney damage, which affects his ability to pursue treatments that require full kidney function.
● Has had 5 operations since February 2023 to replace the ureter stent used to preserve as much kidney function as possible.
● In April 2024 the cancer spread to bone in his spine (the L2 vertebra) leading to a compression fracture and spinal stenosis, requiring surgery to separate his spinal column from the spinal cord. He is recovering from that surgery.

This session also discussed:
- What the BostonGene analysis uncovered
- The treatment options being considered for Brian
- The strategic principles being applied to make a decision on Brian’s next treatment
- Next steps in Brian's treatment

Full transcript: https://docs.google.com/document/d/1s...

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