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Novel potential approaches for treatment of cancers with KRAS mutations: time for reassessment?

last modified Jul 18, 2016 10:27 AM

A recently published paper from the Venkitaraman group has identified new potential avenues for the treatment of certain forms of cancer, which carry mutations affecting the KRAS gene.

Approximately 25% of all human cancers carry KRAS gene mutations. These include most pancreatic cancers, as well as many cancers of the lung and colon. It has recently been suggested that drugs that interfere with cell division (anti-mitotic drugs) selectively kill KRAS-mutant cancer cells. This idea is being tested in clinical trials.

Dr David Perera and Prof Ashok Venkitaraman have found that mutations in KRAS alone do not predict whether cancer cells will respond to anti-mitotic drugs. Instead, contrary to expectations, high expression of a second cancer-causing gene, c-MYC, cooperates with KRAS mutations to determine responsiveness. The study, entitled ‘Oncogenic KRAS triggers MAPK-dependent errors in mitosis and MYC-dependent sensitivity to anti-mitotic agents’ was recently published in Scientific Reports.

Dr David Perera, first author on this study, commented: "Our findings caution against the use of KRAS mutation alone as a biomarker predictive of response to anti-mitotic drugs such as paclitaxel, a drug which is currently used in the clinic for the treatment of several types of cancer. However, we suggest that high expression of a second cancer-causing gene, c-MYC, may cooperate with KRAS mutations to determine responsiveness.”

This study suggests that drugs targeting the cooperation between c-MYC and mutant KRAS could provide new approaches to treat pancreatic, lung or colon cancers. “Our study opens up new avenues to therapeutically target KRAS-mutant tumours and to stratify patients in ongoing clinical trials of anti-mitotic drugs.”

Publication Details:

Perera D and Venkitaraman AR. Oncogenic KRAS triggers MAPK-dependent errors in mitosis and MYC-dependent sensitivity to anti-mitotic agents. Sci Rep (2016). DOI: 10.1038/srep29741

Further information on research carried out by the Venkitaraman group can be found here.