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In October, PCF convened the 27^th annual Scientific Retreat – our first virtual Retreat ever! With no constraints of time or geography, more than 1000 leading prostate cancer researchers registered to attend. From the two days jam-packed with talks and discussion about the latest in prostate cancer science and treatments, we’ve distilled the Top 5 stories for our readers.

Can CAR T Cells Fight Prostate Cancer?

Tanya Dorff, MD

T cells are key players in the body’s immune response. Their job is to recognize and directly kill “dangerous” cells infected by a virus or bacteria or that have become cancerous. They can now be engineered in a lab to fight prostate cancer with the addition of a chimeric antigen receptor (CAR) that can recognize PSCA, a protein on the surface of prostate cancer cells. This allows us to arm the body’s own natural defense mechanisms to kill the cancer cells, much like it would fight any other invader.

Dr. Tanya Dorff is on the cutting edge of this research, advancing this approach through early-phase clinical trials. Already, there are promising results: one patient with metastatic prostate cancer and a rising PSA had a dramatic drop in PSA upon treatment with CAR T cells.  CAR T cells have been highly successful against certain types of leukemias and lymphomas, and we now see a signal that CAR T cells may also have the potential to put prostate cancer patients into remission. Although we have a lot more to learn about them and managing their side effects, this is hopeful news that in the future we will have a ”personalized immunotherapy” option for patients whose disease has progressed on other therapies.

Unlocking the King of All Cancer Proteins

Sarki Abdulkadir, MD, PhD

MYC is a protein that is involved in up to 70% of all cancers. Some have called it a “master oncogene” due to its critical roles in cell metabolism and growth. MYC is commonly thought to be “undruggable,” as its highly disordered structure does not allow for many locations where a treatment might attach and limit its activity. However, Dr. Sarki Abdulkadir and his team are beginning to prove otherwise, as they have found several small molecules with the ability to bind to MYC. Through rapid testing in mice, several compounds were found that could not only bind and disrupt MYC, but also promote the breakdown of the protein, as well as activate the immune system. The importance of this development cannot be understated, in that PCF Team Science Challenge Award researchers have found a candidate drug for one of the most important targets in all of oncology – a challenge that has eluded large biotech and pharmaceutical firms for decades. Further preclinical studies are now underway in order to ready this exciting new treatment for testing in clinical trials.

Testing a New Treatment for Metastatic CRPC

Matthew Rettig, MD

There is a crucial need for effective treatments for metastatic castration-resistant prostate cancer (mCRPC). One option involves immunotherapy, using the body’s natural T cells to recognize, bind to, and kill cancer cells. Bispecific T-cell engagers (BiTEs) are specially-designed antibody-based chimeric proteins that can bind to T-cells and tumor cells simultaneously. (Yes, “chimeric” is the technical term. Imagine the chimera monster from Greek mythology, composed of a lion, a goat, and a snake – but much, much smaller.) When these treatments are infused into the patient, they find their way to the tumor, bringing the T cells with them.

An early phase trial by Dr. Matthew Rettig and team has found sustained positive responses in patients with mCRPC, with some patients even continuing to undergo treatment for more than 6 months. Large reductions in PSA were seen in the majority of cases, all of whom were previously not responding to multiple types of therapy.  Overall, the treatment had a manageable safety profile as a single therapy. This trial is continuing to accrue patients, and is also beginning to test the efficacy and safety of this treatment in combination with the checkpoint immunotherapy pembrolizumab.  Through initial testing, BiTEs have been shown to be a potentially viable option for mCRPC patients, illuminating another path toward disease control.

Biopsies Without a Needle

Gerhardt Attard, MD, PhD

No one wants a prostate biopsy, but it’s currently the gold standard for prostate cancer diagnosis. For men with metastatic disease, if a biopsy is needed to look at changes in the cancer at distant sites in the body, it can be especially challenging. A “liquid biopsy” that would allow doctors to look at prostate cancer markers in blood has been the “holy grail” for years. Today, there are FDA-approved tests using circulating tumor DNA (ctDNA) as a liquid biopsy: DNA that has been released by tumor cells into the circulation and can be collected from patients by blood draws. Researchers are studying how change in the genetic material in ctDNA can be used as a biomarker to measure disease burden and predict patient outcomes.

PCF researchers expert on ctDNA have discovered a way to greatly improve on this method of liquid biopsies. Dr. Gerhardt Attard and his team are analyzing a modification of ctDNA known as a methylation pattern – rather than focusing on the DNA itself – which is better at indicating tumor burden than ctDNA levels alone. Their results suggest that this approach is superior in a number of ways and may be at the next “bleeding edge” of liquid biopsy science. While this technology is still in development, in the future, ctDNA methylation may be used to better classify prostate cancer for precision care.

Current Challenges in Treatment of Patients With Metastatic Prostate Cancer

Himisha Beltran, MD

In a survey of patients and advocates who attended the 27^th Annual PCF Scientific Retreat, many expressed interest in learning more about Dr. Himisha Beltran’s talk on treatments for metastatic prostate cancer.

Despite years of research, many recent advances, and reports of “exceptional responders,” metastatic prostate cancer kills more than 30,000 men in the US each year, and many more globally. Dr. Beltran described one unique approach to researching the problem: the PCF N=1 Natural History Study. This is a highly collaborative, multi-institutional study that will facilitate data collection on patients with specific mutations in their tumors treated with experimental cancer therapies or who exhibit “exceptional” (read: exceptionally good or exceptionally bad) responses to standard of care treatments. With enough data, researchers may be able to uncover patterns that they would not see by looking at just a few patients, and use this information to design new precision medicine clinical trials and treatments.

Also crucial to attacking metastatic prostate cancer are biomarkers: characteristics of cancer that can be measured and used to describe the extent and severity of the cancer, predict patient response and/or to guide choice of therapy. Such is the crux of precision medicine: identifying the right patient (using biomarkers) for the right drug at the right time. One important and promising biomarker is prostate-specific membrane antigen (PSMA), found on the surface of prostate cancer cells. Many emerging therapies targeting PSMA, using a variety of approaches, are working their way through clinical trials.

Finally, resistance to androgen therapy is a hallmark of many metastatic tumors. Researchers are working to identify the underlying mechanisms of this and to design new treatments (or combinations of treatments). As just one example, early phase clinical trials of drugs targeting a specific molecule on the surface of neuroendocrine prostate cancer (a highly aggressive form) are underway. In the next 5 to 10 years, Dr. Beltran envisions that we will know how to better use existing biomarkers to assess patients, and we will also have new biomarkers. New targets for drugs, and new drugs with novel mechanisms, will get us that much closer to the goal of zero deaths from prostate cancer.