AsianScientist (Jan. 13, 2016) – A study by Singapore researchers has demonstrated the effectiveness of a small molecule drug, PRIMA-1met, at inhibiting the growth of colorectal cancer cells by activating a tumor suppressor gene, mutant p53, without damaging DNA in the process. The article was published in the journal Oncotarget.
PRIMA-1met is a compound that has been shown in previous studies to activate mutant p53 and promote cancer cell death. The compound has also demonstrated promising preclinical activity in various cancer types and has a good drug safety profile.
In this study, the research team from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore found PRIMA-1met to be most effective at killing colorectal cancer cells that contain the mutated p53.
Unlike most anti-cancer drugs that work by inducing damage to DNA—and which often have serious side effects—PRIMA-1met is more favorable as it restores the structure and function of the mutated p53 gene, which is also known as the “guardian of the genome.”
p53 codes for an important protein that helps to stabilize and repair genomes. When mutations occur in p53, the cells become more susceptible to damage and hence turn cancerous. Nearly half of colorectal cancer patients have mutations in the p53 gene.
“Colorectal cancer is known for its poor long-term survival rates among adults,” said Professor Chng Wee Joo, deputy director and senior principal investigator at CSI Singapore, who led the research.
“Given the safety profile of PRIMA-1met, coupled with its minimal and fully reversible side effects, we are optimistic that the development of this drug as a targeted therapeutic approach against colorectal cancer, together with chemotherapy, holds good potential for patients.”
Currently, PRIMA-1met is part of a Phase I/II clinical trial in hematologic malignancies and prostate cancer. In the future, Chng and his team plan to test if the combination of PRIMA-1met with anticancer drugs such as Fluorouracil and Oxaliplatin, which are commonly used for the treatment of colorectal cancer, will optimize the results of chemotherapy.
The article can be found at: Li et al. (2015) PRIMA-1met (APR-246) Inhibits Growth of Colorectal Cancer Cells with Different p53 Status Through Distinct Mechanisms.
———
Source: National University of Singapore; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
