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National Cancer Centre Singapore scientists discover p53 mutation hinders cancer treatment response
Date:1/25/2013

tant p53 have DN effects in a cell-type and dose-dependent manner, especially during acute p53 activation where p53 levels are elevated. Based on the above observations, efforts to generate specific inhibitors for the common hot spot p53 point mutations are underway. The inhibition of mutant p53 expression in cells carrying a wild-type and mutant p53 alleles can improve response to chemotherapeutic drugs.

In a further study, the researchers also questioned the possibility of the mutant p53 acquiring new functions (or Gain of Function) to drive carcinogenesis, transforming normal cells to cancerous cells. Their investigation comparing cells from genetically engineered mouse strains expressing 2 different types of p53 mutations: the R172H mutation versus the R246S mutation, which showed that Gain of Function (GOF) was found only in the former. This showed that GOF of mutated p53 is specifically dependent on mutation-type but not across all kinds of genetic mutations, highlighting diversity in properties of the different types of p53 mutations, thereby indicating that mutations found in human cancers can behave differently, and thus, need to be carefully assessed prior to treatment.

Thus, the existence of mutant p53 certainly has a negative impact on cancer treatment, whether it is through DN effect or GOF. Prof Sabapathy said that the team is now embarking on more research to determine the possibility of targeting mutant p53 without affecting wild-type p53 in human cells, paving way to clinical trials in the future to test the efficacy on cancer therapeutic response.


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Contact: Rachel Tan
Rachel.Tan.C.H@nccs.com.sg
65-623-69535
SingHealth
Source:Eurekalert

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