Rakesh Singal, M.D.
Associate Professor of Medicine
Description of Research
Research in Dr. Singal’s laboratory has focused on understanding epigenetic mechanisms of gene silencing in cancer, identification of gene targets, and use of epigenetic therapy to reverse drug resistance. Dr. Singal has identified the role of GADD45a, a pro-apoptotic gene, in docetaxel mediated cytotoxicity and identification of this gene as a potential therapeutic target in prostate cancer. This preclinical study led to the pioneering Phase I/II study clinical trial to study the safety and efficacy of azacitidine and docetaxel in metastatic castration resistant prostate cancer patients.
Other research activities include identification of non-invasive biomarkers for prostate cancer detection and diagnosis. The major problem associated with PSA screening for prostate cancer is low specificity. Only 25-35% of men who are identified as patients with intermediate risk for prostate cancer are diagnosed with prostate cancer after a biopsy. This means that a large proportion of the intermediate risk group patients are subjected to unnecessary prostate biopsy. Dr. Singal’s study examined the usefulness of fcDNA analysis in a typical prostate cancer screening setting and showed that high fcDNA levels were significantly associated with prostate risk and improved the specificity of PSA. Hence, fcDNA may be a reliable predictor of prostate cancer and may reduce the number of unnecessary biopsies.
Dr. Singal also collaborates with other investigators in the Cancer Center in other areas such as pancreatic cancer, lung cancer, and lymphoma.
Clinical Research: Dr. Singal’s clinical research focuses on genitourinary malignancies. He is the principal investigator (PI) of a Phase I/II Study of azacitidine (Vidaza), docetaxel (Taxotere) and prednisone for patients with hormone refractory metastatic prostate cancer previously treated with a taxotere-containing regimen. This is the first clinical trial to study the safety and efficacy of azacitidine and docetaxel when given together with prednisone in metastatic docetaxel refractory CRPC patients. He is also the local PI of multicenter study investigating the role of novel agents in the treatment of prostate cancer. He also participates in other ongoing clinical trials at the Cancer Center.
- Dr. Singal and his research team discovered that GADD45a, a gene involved in apoptosis, plays an important role in docetaxel-mediated apoptosis in prostate cancer cells. Activation of this gene led to enhanced sensitivity to docetaxel treatment indicating that GADD45a is a potential therapeutic target in prostate cancer.
- Dr. Singal’s research showed that free circulating DNA may improve the specificity of prostate cancer screening. The study shows that adding free circulating DNA to prostate cancer screening can reduce the number of unnecessary prostate biopsies and thus have a significant impact in reducing patient discomfort and health care costs.
- Dr. Singal has completed the Phase 1 portion of the Phase I/II Study of Azacitidine (Vidaza), Docetaxel and Prednisone for Patients With Hormone Refractory Metastatic Prostate Cancer Previously Treated With a Taxotere Containing Regimen. The results showed that the combination was safe and active in patients with metastatic castration resistant prostate cancer. The Phase 2 portion of the study is currently ongoing.
Selected Cancer-Related Publications
- Ramachandran K, Gopisetty G, Gordian E, Navarro L, Hader C, Reis IM, Schulz WA, Singal R. Methylation-Mediated Repression of GADD45alpha in Prostate Cancer and Its Role as a Potential Therapeutic Target. Cancer Res 69:1527-1535, 2009. Read more »
- Gordian E, Ramachandran K, Singal R. Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity. Anticancer Res 29:3207-10, 2009. Read more »