The discovery of a novel target in castration-resistant prostate cancer (CRPC) and the potential of drugs targeting this to delay or overcome adaptive resistance is the subject of today’s post.
Followers of the prostate cancer field know that one of the challenges with drugs such as enzalutamide and abiraterone is that patients stop responding to them over time and they develop acquired resistance.
So imagine that you could give a drug that is not only an effective anti-cancer agent in patients with acquired resistance, but might then allow those treatments to be effective a second time around. A recently identified druggable target means this is now a possibility.
Of course, it’s early days yet, and the preclinical work has yet to translate into humans, but it’s not hard to see the commercial implications in the prostate cancer landscape for companies such as $MDVN, $JNJ, $TKAI, Bayer and anybody else who wants to be a player.
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San Francisco – In the ASCO GU prostate cancer session yesterday morning one of the most interesting presentations was by Andrew J Armstrong, Associate Professor of Medicine and Surgery at the Duke Cancer Institute.
I previously referenced Dr Armstrong’s excellent education presentation at ASCO 2012 in my piece on Xconomy about the emerging challenges of prostate cancer drug development.
He’s a speaker that I particularly enjoy listening to, so my attention was immediately drawn to his presentation at ASCO GU on, “Beyond Enzalutamide and Abiraterone: What’s Next in Androgen Therapy.”
Looking at this title, at first glance the question that comes to mind is do we really need new treatments that target the Androgen Receptor (AR), after all we’ve heard this week about the PREVAIL trial with enzalutamide?
Based on Dr Armstrong’s presentation the answer is a resounding yes!
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A scientific meeting that I would have liked to have attended and one where I think attendees will obtain a lot of insight into the future of prostate cancer research is the forthcoming American Association for Cancer Research (AACR) Advances in Prostate Cancer Research meeting.
Chaired by Charles Sawyers (MSKCC) and Arul Chinnayan (Michigan) it has an impressive line-up of speakers and sessions. The meeting takes place next week (Feb 6-9) in Orlando.
There are two presentations on cabozantib (XL184) that may offer new insights into the mechanism of action of the drug and its potential:
Cabozantinib (XL-184) and prostate cancer: Preclinical and clinical profile of a novel agent
Maha Hussain, University of Michigan Medical School, Ann Arbor, MI
Cabozantinib (XL184) inhibits androgen-sensitive and castration-resistant prostate cancer in the bone and increases bone formation in non-tumored bones
Eva Corey, University of Washington, Seattle, WA
A few of the presentations at the meeting that caught my attention include:
- Role of inflammation (William Nelson)
- Influence of tumor microenvironment on progression and resistance (Christopher Logothetis),
- Novel therapeutic targets in prostate cancer (Arul Chinnaiyan)
- Overcoming castration-resistant prostate cancer
If you have in an interest in prostate cancer research, February 6-9 in Orlando is the place to be.
The recent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics international conference in San Francisco was an informative meeting.
What I particularly liked was the strategic overview that took place in many of the plenary sessions.
As an example, Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research/The Royal Marsden in London highlighted the potential drug development targets based on prostate cancer biology:
- Androgen Receptor (AR)
- Heat Shock Proteins (Hsp)
- Signaling: HER3, MET, IGF-1R, CCL2, IL-6, Src
- PI3K/AKT/TOR signaling
- PARP and BRCAness
- Estrogen receptor (ER)
- c-MYC & CHK1
His presentation discussed the possible therapeutic approaches, and complexity involved in developing novel targeted therapies for prostate cancer.
This is something that I expect we will hear more of at the AACR special conference on Advances in Prostate Cancer Research early next year.
In particular, de Bono discussed drug development strategies to target androgen receptor signaling, and some of the future challenges including:
- Proving to the regulatory authorities that circulating tumor cell (CTC) count falls are a robust immediate endpoint of overall survival
- Developing improved imaging for bone metastases
As a side note, there were several posters for cabozantinib (XL184) at the meeting (available on the Exelixis website), including preliminary research on computer-aided quantitative bone scan assessment.
However, as de Bono mentioned in his presentation, “diffusion weighted MRI shows hot spots not detected by bone scans.”
2010 and 2011 were good years for prostate cancer drugs, and with new approvals for MDV3100 and radium-223 (Alpharadin) expected, 2012 is set to be another “grand cru” year, to paraphase Bertrand Tombal.
If you were not able to make it to San Francisco for the Molecular Targets and Cancer Therapeutics conference, webcasts of many sessions will be available on the AACR site.