Adam Weiner, MD

Adam Weiner, MD, chief urology resident at Northwestern University in Chicago, UCLA Urology, discusses the results of his research on molecular subtyping in prostate cancer.

data given by Weiner at the 2022 American Urological Association Annual Meeting

, there was a good amount of overlap when directly comparing this research to the PAM50 model. This included luminal-differentiating tumors having the highest AR-activity scores, and luminal proliferating tumors having the highest expression of AR and cell proliferation genes and pathways.

Additionally, basal immune tumors had the highest predicted response rate to radiation and possessed significant immune infiltration. Basal neuroendocrine tumors were also characterized by low AR-activity expression, low immune infiltration, and enrichment with neuronal gene expression.

According to Weiner, the next step will be to examine clinical data regarding how luminal cells respond to docetaxel or how basal cells respond to androgen deprivation.

0:08 | We presented our preliminary approach. We've completed the creation of the signature and now, we're looking at the relevant, different markers based on the 4 subgroups created by the signature, all of which are basal versus luminal cell-of-origin. It's quite striking.

Each subgroup had a specific treatment susceptibility pattern and with that, you could use the information going forward if you have to apply additional treatments following prostatectomy or treatments if the patient has a metastatic recurrence. All of these things could be incredibly useful to practitioners.

The next step is applying this new sub-classifier to clinical data. We've relied on gene expression signatures to preliminarily show the treatment susceptibilities based on the 4 subgroups. The next step is to take clinical data and see how the luminal cells respond to docetaxel or how the basal cells respond to androgen deprivation. Which group of tumors are the most likely to respond to radiation therapy? I think if we can show that, we can show that using a signature based on cell-of-origin is something worth our time.

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Adam Weiner, MD, discusses the results of his research on molecular subtyping in prostate cancer.









Research Explores Molecular Subtyping in Prostate Cancer.

Adam Weiner, MD, chief urology resident at Northwestern University in Chicago, discusses the importance of molecular testing for prostate cancer and what the current targeted therapy landscape looks like for this disease.

Prostate cancer has been subclassified based on molecular drivers. However, utility remains limited due to the reliance on multi-omics and cost and while commercial products have been widely used for this implication, they do not subclassify prostate cancer regarding molecular subtypes.

Since there are no studies which aim to create a prostate-specific model based on cell-of-origin, Weiner et al developed and validated an RNA expression-based prostate cancer subtyping classifier for cell-of-origin expression patterns which was created with the help of the originators of the GRID cohort (NCT02609269). Two cohorts were examined, including a training cohort which consisted of 32,000 patients and a validation cohort of 68,547 patients.

Currently, there are many commercial products out there that can help us prognosticate prostate cancer and they're certainly adding to our ability to personalize prostate cancer management. At this point, we're still working towards a perfect subtyping mechanism for prostate cancer that can really distill what treatment makes sense for which patients. I think right now we have great tests that can help us determine the aggressiveness of prostate cancer or who needs to be monitored more closely, but we're still working on a great subtyping mechanism to figure out how we can personalize treatment.

There is a lot of research out there that has looked at subtypes of prostate cancer, though in large part, it's been limited in terms of its ability to be applied clinically, and that's for many reasons. They use a multi-omics approach that might not be available on a wide enough scale, or the cost might not be something that can be incurred by all the patients in the providers. We are still looking for something that can be applied more broadly.

Adam Weiner, MD, discusses the importance of molecular testing for prostate cancer and what the current targeted therapy landscape looks like for this disease.

Adam Weiner, MD | Authors

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Research Explores Molecular Subtyping in Prostate Cancer.

Importance of Molecular Testing in Prostate Cancer