Advancing Prostate Cancer Treatment

With 29 000 men dying annually, effective and safe drug therapy as a prostate cancer treatment is crucial.¹ Thankfully, a new clinical trial shows promise.

Most cancers spread in two ways and are labelled non-metastatic and metastatic. Non-metastatic cancer is more restricted than metastatic spreading in a linear fashion. Compared to non-metastatic, metastatic cancers spread more freely and sporadically and has a high mortality rate. The metastatic type is aggressive, spreading throughout the whole body, not just the initial affected area. Prostate cancer is typically non-metastatic but if left untreated, can become metastatic.

The standard prostate cancer treatment has been to reduce the amount of androgen hormones (androgen deprivation therapy) while also providing chemotherapy.¹ However, some types of prostate cancer cannot be controlled even through hormone therapy; this type is known as metastatic castration-resistant prostate cancer (mCRPC). 

Scientists have conducted a study testing the effectiveness of drug therapy using rucaparib, a drug known for its positive effects on ovarian cancer, to treat mCRPC.² 

Rupacarib as an Anti-Tumor Drug

Rupacarib has become many researchers’ drug of choice for prostate cancer treatment as it inhibits an enzyme that blocks a cells ability to repair DNA while also providing stability to a DNA strand.³ The drug stops the enzyme action of polyadenosine diphosphate ribose polymerase (PARP), preventing cancer cells from healing themselves and spreading. 

The pharmaceutical has shown effectiveness in previous clinical trials fighting against mutations leading to ovarian cancer. Additionally, reported adverse events were not serious or unexpected and were primarily nausea, vomiting, fatigue, and anemia, all of which were easily managed.³ 

TRITON Trials

Scientists have located two genes BRCA1 and BRCA2 involved in cancer risk.³ Mutations in these genes can affect if cancer becomes a diagnosis and what the outcome of treatment and survivability may be. The TRITON clinical trial primarily explores if rucaparib can halt prostate cancer progression.

In phase II of the clinical trial, around 12% of men with mCRPC have a deletion or alteration of the BRCA gene.⁴ This gene alteration means that patients receiving rucaparib treatment were experiencing anti-tumor activity.⁴ The anti-tumor activity was confirmed with radiographs, and progression to phase III of the trial was approved.⁴

Future Research 

Phase III of the TRITON trial is estimated to wrap up in March 2023. Scientists and healthcare providers are hopeful that rucaparib will be approved as a standard prostate cancer treatment as adverse events were mild to moderate in intensity. However, future research should look into finding markers of PARP activity and create an approach to inhibit its activity when undergoing chemotherapy or radiotherapy. 

References 

1. Chandrasekar, T., Yang, J. C., Gao, A. C., & Evans, C. P. (2015). Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Translational Andrology and Urology, 4(3), 365–380. https://doi.org/10.3978/j.issn.2223-4683.2015.05.02
2. Ryan, C. J., Watkins, S. P., Despain, D., Karlovich, C. A., Simmons, A., Golsorkhi, A. A., & Chowdhury, S. (2017). Trial of rucaparib in prostate indications 3 (TRITON3): An International, Multicenter, randomized, open-label phase 3 study of Rucaparib vs physician’s choice of therapy for patients (PTS) with metastatic castration-resistant prostate cancer (MCRPC) associated with homologous recombination deficiency (HRD). Journal of Clinical Oncology, 35(15_suppl). https://doi.org/10.1200/jco.2017.35.15_suppl.tps5087 
3. Colombo, I., Lheureux, S., & Oza, A. M. (2018). Rucaparib: A novel PARP inhibitor for BRCA advanced ovarian cancer. Drug Design, Development and Therapy, Volume 12, 605–617. https://doi.org/10.2147/dddt.s130809 
4. Abida, W., Patnaik, A., Campbell, D., Shapiro, J., Bryce, A. H., McDermott, R., Sautois, B., Vogelzang, N. J., Bambury, R. M., Voog, E., Zhang, J., Piulats, J. M., Ryan, C. J., Merseburger, A. S., Daugaard, G., Heidenreich, A., Fizazi, K., Higano, C. S., Krieger, L. E., … Chowdhury, S. (2020). Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. Journal of Clinical Oncology, 38(32), 3763–3772. https://doi.org/10.1200/jco.20.01035