Journal
BRITISH JOURNAL OF CANCER
Volume 114, Issue 6, Pages 638-641Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2016.49
Keywords
BH3 profiling; A-1331852; A-1210477; ABT-199; MCL-1; BCL-XL
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Funding
- NorthWest Cancer Research (NWCR) [CR994]
- Medical Research Council [MC_U132615750] Funding Source: researchfish
- MRC [MC_U132615750] Funding Source: UKRI
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Background: Anti-apoptotic BCL-2 family members antagonise apoptosis by sequestering their pro-apoptotic counterparts. The balance between the different BCL-2 family members forms the basis of BH3 profiling, a peptide-based technique used to predict chemosensitivity of cancer cells. Recent identification of cell-permeable, selective inhibitors of BCL-2, BCL-X-L and MCL-1, further facilitates the determination of the BCL-2 family dependency of cancer cells. Methods: We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of cancer cells. Results: Both BH3 profiling and the inhibitor toolkit effectively predict chemosensitivity of cells addicted to a single anti-apoptotic protein but a combination of both techniques is more instructive when cell survival depends on more than one anti-apoptotic protein. Conclusions: The inhibitor toolkit provides a rapid, inexpensive and simple means to assess the chemosensitivity of tumour cells and in conjunction with BH3 profiling offers much potential in personalising cancer therapy.
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