Thousands of researchers, clinicians, advocates, and industry partners gathered in Orlando earlier this month for the American Association for Cancer Research (AACR) Annual Meeting 2023. Meeting sessions addressed themes across all cancer, including basic biology and genetics research, clinical trials, survivorship, prevention and early detection, and global health.
More than 35 PCF-funded studies and investigators were represented. Below are three examples of cutting-edge findings in prostate cancer from PCF-supported researchers.
- A new biomarker to identify aggressive prostate cancer
- A large study of men of African ancestry reveals genes that increase risk of prostate cancer
- An early-phase clinical trial of a new “smart bomb” therapy
A novel biomarker may help to predict patient outcomes
Accurate biomarkers (measurable features of a cancer) are needed to provide information about the likely course and outcome of advanced prostate cancer. Chromosomal instability (CIN) describes changes in the numbers and structure of chromosomes (packets of genetic material) found in cancer cells. PCF-funded researchers studied CIN in 304 biopsy samples from men with aggressive prostate cancer and linked their findings to clinical outcomes.
The results showed that CIN was associated with other genetic mutations that are known to confer treatment resistance and poor outcomes. CIN was not influenced by prior treatment with novel hormonal therapies or with taxane chemotherapy. CIN was linked to worse overall survival regardless of age, disease state, or other genetic mutations: patients with high CIN were three times more likely to die.
What this could mean for patients: Early research suggests that a measure called chromosomal instability seen in prostate biopsy tissue may predict patient survival. More research is needed to confirm these findings and to identify potential approaches to treatment.
RESPOND study identifies prostate cancer risk genes in men of African ancestry
RESPOND is a large study that aims to identify the environmental and genetic factors related to disproportionately high diagnoses of aggressive prostate cancer in African American men.
Certain rare, inherited gene mutations are known to increase a man’s risk of prostate cancer, especially of aggressive disease. Researchers analyzed data from RESPOND to understand the significance of 36 genes and their effect on prostate cancer risk in 12,000 men of African ancestry.
Harmful or potentially harmful inherited gene mutations were rare: the gene most frequently affected was the BRCA2 gene, with mutations found in 1.7% of men with prostate cancer of any stage and in 1.1% of men without the disease. Other genes less commonly affected were MUTYH (1.5% cases/1.3% non-cases), ATM (0.93%/0.49%), MSH5 (0.70%/0.51%), and HOXB13 (0.70%/0.35%).
Certain genes were linked to increased risk of prostate cancer overall. For example, men with mutations in the ATM gene were 83% more likely to be diagnosed vs. those without ATM mutations, and men with mutations in BRCA2 were 52% more likely to be diagnosed. Men with mutations in the PALB2 gene were over 3 times more likely to be diagnosed. (Of note, mutations in PALB2 were very uncommon.)
Gene mutations also influenced the severity of prostate cancer. Among men in the study with prostate cancer, those with mutations in the ATM gene were 5 times more likely to have aggressive disease (vs. non-aggressive disease). BRCA2 and PALB2 mutations were also linked to increased risk of aggressive disease.
What this means for patients: The study confirms that it is important to know how inherited gene mutations may affect risk of prostate cancer among men of African descent. Have an open discussion with your family about all cancer diagnoses, not just prostate cancer. Talk to your doctor about screening, early detection, and possible referral to a genetic counselor. Read more on screening and family cancer risk.
Early-phase study of a novel targeted therapy for advanced prostate cancer shows promising results
In 2022, the first radionuclide therapy was approved for patients with metastatic castration resistant prostate cancer (mCRPC). It works like a “smart bomb” by targeting a molecule called prostate-specific membrane antigen (PSMA) on the surface of prostate cancer cells, delivering a small amount of radiation to those cells wherever they are in the body. Other forms of radionuclide therapy are being developed, using different molecules to target PSMA and different radioactive particles. A PCF-funded phase I/II clinical trial tested safety and preliminary efficacy of a therapy called 225Ac J591, in which J591 is the binding molecule and Actinium-225 is the radioactive particle.
24 patients with mCRPC were enrolled. 53% had received previous treatment with a novel hormonal therapy and 58% with taxane chemotherapy. In terms of safety, few serious adverse events were seen. There were 3 cases of dose-limiting toxicity as defined by the study protocol. The most common low-grade, non-hematologic adverse events associated with treatment were fatigue (95%), dry mouth (69%), and nausea (57%). Substantial drops in PSA levels were noted: 95% of patients had PSA decline. Two-thirds of these patients saw their PSA decline by 50%, and 37% of patients had a PSA decline of 90%. Early efficacy was also observed by decreases in circulating tumor cells.
What this could mean for patients: New therapies for mCRPC are urgently needed. Different types of radionuclide therapy may offer advantages for certain patients. In the future, if larger, randomized clinical trials of 225Ac J591 are successful, patients may have an additional treatment option.