“In a way, the cancer cells self-implode because the exposure to the drug activates the mechanism in the cancer cell that actually kill the cells on its own,” said Professor Chng Wee Joo, a senior principal investigator at the Cancer Science Institute of Singapore.
As much as, 900 patients die from colorectal cancer annually in Singapore. Contributing up to 14 % of all cancers in Singapore, the colorectal cancer (also called as colon cancer, rectal cancer or bowel cancer), primarily affects parts of the large intestine (colon and rectum).
However, a recent study by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has demonstrated the potential of a small molecule drug, which when combined with chemotherapy is likely to benefit colorectal cancer patients in a synergistic manner. Supported by grants from the National Research Foundation Singapore, Ministry of Education and the National Medical Research Council the NUS research team published their work in the journal Oncotarget (October 2015).
Once deemed as too weak for use, this decade old drug PRIMA-1met has demonstrated significant efficiency in inhibiting the growth of colorectal cancer cells. Previous studies on the drug have shown it capable of activating the mutant p53, a tumor suppressor gene, and adept at promoting cancer cell death. Also known as the “Guardian of the genome”, p53 gene codes for an important protein that helps to stabilize and repair genomes. That makes mutations in this gene all the more perilous. The cells become more vulnerable to damage and turn cancerous. Studies have shown that as much as 50% of colorectal cancer patients have mutations in the p53 gene.
The findings by the NUS team demonstrate PRIMA-1met to be highly effective in targeting and killing colorectal cancer cells containing the mutated p53 gene. The PRIMA-1met restores the structure and function of the mutated p53 gene while specifically promoting cancer cell death. This makes the drug considerably more favorable, than most anti-cancer drugs which function by inducing significant DNA damage with considerable side effects.
Currently, having demonstrated favorable preclinical activity and drug safety profiles, the PRIMA-1met is part of Phase I/II clinical trials on hematologic malignancies and prostate cancer in Europe. The drug is being tested for its safety and efficacy, as well as effective dosage range and potential side effects on groups of patients.
Whilst in Singapore, despite having done only in vitro studies at the moment, Prof Chng is optimistic about the drug’s potential for a targeted therapeutic approach in treating colorectal cancer, alongside chemotherapy. In the future, Prof Chng and his team plan on testing and optimizing combinations of PRIMA-1met and common colorectal cancer treatment drugs (ex: Fluorouracil and Oxaliplatin) with chemotherapy.