Journal article

PLX8394, a new generation BRAF inhibitor, selectively inhibits BRAF in colonic adenocarcinoma cells and prevents paradoxical MAPK pathway activation

Candani SA Tutuka, Miles C Andrews, John M Mariadason, Paul Ioannidis, Christopher Hudson, Jonathan Cebon, Andreas Behren

MOLECULAR CANCER | BIOMED CENTRAL LTD | Published : 2017

Abstract

BRAF inhibitors (BRAFi) are standard of care for the treatment of BRAF V600 mutation-driven metastatic melanoma, but can lead to paradoxical activation of the mitogen-activated protein kinase (MAPK) signalling pathway. This can result in the promotion of precancerous lesions and secondary neoplasms, mainly (but not exclusively) associated with pre-existing mutations in RAS genes. We previously reported a patient with synchronous BRAF-mutated metastatic melanoma and BRAF wt /KRAS G12D-metastatic colorectal cancer (CRC), whose CRC relapsed and progressed when treated with the BRAF inhibitor dabrafenib (GSK2118436). We used tissue from the resected CRC metastasis to derive a cell line, LM-COL-1..

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University of Melbourne Researchers

Grants

Awarded by National Health & Medical Research Council of Australia Postgraduate Research Scholarship (NHMRC)


Awarded by NHMRC Research Fellowship


Funding Acknowledgements

This research was supported by a Melanoma Research Alliance Team Science Award to JC and in part by Operational Infrastructure Support Program Funding of the Victorian State Government for the Ludwig Institute for Cancer Research. AB is supported by a Cancer Council Victoria grant, MCA is supported by a National Health & Medical Research Council of Australia Postgraduate Research Scholarship (NHMRC# 1055456), and JMM is supported by a NHMRC Research Fellowship (APP1046092).