Mutations in specific codons of the KRAS oncogene are associated with variable resistance to neoadjuvant

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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

Marjun P Duldulao1, Wendy Lee, Rebecca A Nelson

  • 1Department of Surgery, City of Hope, Duarte, CA, USA.

Annals of Surgical Oncology
|March 5, 2013
PubMed
Abstract

Insights

Specific KRAS mutations, particularly in codon 13, are linked to poor response in rectal cancer patients undergoing chemoradiation therapy (CRT). These mutations also correlate with TP53 mutations, impacting treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • KRAS and TP53 mutations are common in colorectal cancer and linked to therapy resistance.
  • Rectal cancers with both KRAS and TP53 mutations show reduced response to neoadjuvant chemoradiation therapy (CRT).
  • The impact of specific KRAS mutations on CRT response in rectal cancer is not well understood.

Purpose of the Study:

  • To correlate specific KRAS mutations with rectal cancer response to CRT.
  • To investigate if KRAS mutation-specific correlations with CRT response are influenced by concurrent TP53 mutations.

Main Methods:

  • 148 stage II-III rectal cancer patients received neoadjuvant CRT followed by surgery.
  • Tumor biopsy DNA underwent KRAS and TP53 genotyping.
  • Specific KRAS mutations were analyzed for correlation with tumor response and TP53 co-mutation.

Main Results:

  • 60 patients had KRAS mutations (12 in codon 13, 48 elsewhere); 80 had TP53 mutations.
  • Any KRAS mutation was associated with lower pathological complete response (pCR) rates (p=0.006).
  • KRAS codon 13 mutations showed no pCR (p=0.03) and higher TP53 co-mutation rates (p=0.02).

Conclusions:

  • Different KRAS codon mutations may differentially affect rectal cancer resistance to CRT.
  • Variable resistance to CRT in KRAS-mutant rectal cancers might be linked to differing frequencies of TP53 mutations.

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