Multi-omic Analysis Guides Treatment Decisions for Cancer Patient Lab Co-Founder
“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
Advanced prostate cancer patients want to know what their next treatment option should be if their current regimen fails. However, this is a moving target as new treatments are approved, clinical trials for new treatments begin, and experience is gained in old and new treatments. It is important to occasionally scan the field for 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. In this case study learning session, Dr Rana McKay discusses her interpretation of the test results and considerations of various therapeutic approaches for Cancer Patient Lab co-founder Brian McCloskey .
Dr McKay 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 and novel biomarkers and therapeutic outcomes for patients with genitourinary (reproductive and urinary system) malignancies. Kirill Kryukov presented BostonGene 's analysis of Brian’s cancer, demonstrating the power of transcriptomic (RNA) analysis in identifying key biomarkers.
This is a portion of the Cancer Patient Lab learning session hosted by Brad Power and Brian McCloskey in 2024. The full learning session can be found here on Cancer Patient Lab's YouTube channel, where you can also download the full 60 minute transcript. Join our patient community to access the full library of learning sessions.
Brian was diagnosed in 2016 with stage T2b prostate cancer. He 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. In April 2024 the cancer metastasized to his spine (in the L2 vertebra, the second uppermost of the five lumbar vertebrae toward the lower end of the spinal column, within the lower back) leading to a compression fracture and spinal stenosis (the space inside the backbone is too small) requiring surgery to separate his spinal column from the spinal cord. BostonGene completed extensive testing on Brian’s tumors in early 2024 and identified several targets to pursue.
This is an overview of Brian's cancer journey. There's a primary sample of his prostate from 2016 and on the bottom left, you'll see a secondary sample, which represents the pelvic mass from November of 2022. And this is the footprint for how BostonGene specifically looked at his cancer and thinking about each of the different selective pressures, meaning those systemic therapies, and how they change his cancer over time, and where it stands as of the end of this analysis, which was with a sample tumor, where the pelvic mass was at the end of 2022/early 2023.
BostonGene had two different sample tissues for analysis: the primary tumor sample and a metastatic sample. For both of them, they performed several types of analyses with multiplex fluorescence, their new generation sequencing and IHC tests. From collected blood, they performed immune profiling. With this analysis, BostonGene created an integrated presentation with the most valuable findings
Kirill Kryukov from BostonGene explains "We saw some alterations as the cancer evolved in the second sample, and among them, amplification of androgen receptor, and co-amplification of KIT/PDGFRA/VEGFR2, along with a PTEN gene mutation. This iteration suggests evolutionary divergence and potential targets that may emerge as the disease progresses."
A transcriptomic (RNA) analysis looked for biomarkers that are valuable as antibody-drug conjugates (ADCs bind to the tumor cell, a chemical linker takes a cytotoxic drug inside the tumor cell, which kills the cancer cell while sparing healthy tissue.) for therapy (TROP2, Nectin4, and SLFN11), and all of these markers in both samples demonstrated a medium or a high level of RNA expression. RNA analysis also uncovered a medium or high level of expression of some other potential biomarkers - HER2, HER3, and TGFb.
The immune microenvironment has changed from an immune desert in Brian’s primary prostate sample to fibrotic in his metastatic sample. MxIF analysis, spatial phenotyping, revealed that a lot of the tumor cells demonstrate expression of synaptophysin (a specific and fairly sensitive marker for neuroendocrine tumors of both low and high grades of malignancy) and in the metastatic sample near 38%, and only 3% expression in the primary sample.
Dr McKay commented on the analysis “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.’”
The full learning session can be found here on Cancer Patient Lab's YouTube channel, where you can also download the full 60 minute transcript.
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