Friday, November 15, 2013

Another Potential Treatment for Cancers with p53 Mutations Identified

About half of all cancers are associated with a mutation in a gene called p53 which, in normal cells, is essential for discovering DNA damage and eliminating cells whose DNA damage is too extensive for repair. Just last week we discussed the role of Type 2 PIP kinases in the survival of p53 mutant cancers here. Now another potential target that may enhance treatment of cancers with p53 mutations has been reported!

The image shows cisplatin crystals,
which is a platinum compound,
and used as a chemotherapy drug

Larry Ostby

A recent paper in the journal Cell Reports describes the work of biologists at MIT that found that cancers with mutated p53 could be made more susceptible to chemotherapy if they also lack another gene called MK2. The paper entitled: 'A Reversible Gene-Targeting Strategy Identifies Synthetic Lethal Interactions between MK2 and p53 in the DNA Damage Response In Vivo' describes a study performed in mice where treatment with cisplatin caused dramatic tumor shrinkage when both p53 and MK2 were deleted. Similar treatment of mice with functional MK2 exhibited continued tumor growth. This animal study focused on non-small-cell lung tumors, however, similar results have been observed in cancer cells derived from other tumor types. It is hoped that these results will extend to multiple cancer types and studies are ongoing to investigate mouse models of colon and ovarian cancer.

Since drugs that inhibit MK2 are already available and approved for use to treat inflammatory diseases such as arthritis it is hoped that combining these drugs with current chemotherapy treatments could greatly improve the efficacy of these treatments. The potential combination is not an obvious choice as the usual combinations chosen for cancer treatment each have anti-tumor effects individually, while in this case the MK2 inhibitor does not directly affect cancer growth alone.

Some information for this blog was obtained from the Science Daily article: Biologists ID New Cancer Weakness

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