Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers

Cancer Informatics
Swarnendu TripathiRathindra N Bose

Abstract

Efficacies, toxicities, and resistance mechanisms of chemotherapy drugs, such as oxaliplatin and 5-fluorouracil (5-FU), vary widely among various categories and subcategories of colon cancers. By understanding the differences in the drug efficacy and resistance at the level of protein-protein networks, we identified the correlation between the drug activity of oxaliplatin/5-FU and gene variations from the US National Cancer Institute-60 human cancer cell lines. The activity of either of these drugs is correlated with specific amino acid variant(s) of KRAS and other genes from the signaling pathways of colon cancer progression. We also discovered that the activity of a non-DNA-binding novel platinum drug, phosphaplatin, is comparable with oxaliplatin and 5-FU when it was tested against colon cancer cell lines. Our strategy that combines the knowledge from pharmacogenomics across cell lines with the molecular information from specific cancer cells is beneficial for predicting the outcome of a possible combination therapy for personalized treatment.

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Citations

Dec 12, 2017·Pharmaceutical Patent Analyst·Arindam Sarkar
Nov 20, 2016·International Journal of Pharmaceutics·Larissa KotelevetsPatrick Couvreur
May 1, 2021·International Journal of Molecular Sciences·Donatella VerbanacKarmela Barišić

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Methods Mentioned

BETA
exome sequencing

Clinical Trials Mentioned

NCT02266745

Software Mentioned

COSMIC
MCC
CellMiner

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