Data from a large scale analysis of breast cancer has revealed new targets and new drug possibilities against the disease
For the large scale study, researchers combined data from genetic analyses on multiple breast cancer cell types with new statistical techniques, and compared the information with additional drug data available. Focusing on pathways allowing these cells to proliferate and survive, the study honed in on genes essential to many subtypes like HER2.
"This study represents the largest survey yet of how the genetic changes in breast cancer cells interfere with pathways critical to their growth and survival, pathways that might be targeted by combinations of new or existing drugs. Our new statistical approach represents an improvement on earlier methods that were unable to link the webs of genetic changes in cancer cells to the complex functions on which they most depend"
A big challenge
While treatment has greatly improved, breast cancer remains a significant threat. Its often aggressive nature and large range of potential mutations has made it particular challenging.
The new study performing specific screenings called shRNA screens, on 77 breast cancer cell lines. These screenings involve silencing genes in cancer cells and observing whether they can continue to survive afterwards. By comparing a large number with new statistical techniques, they were able to more accurately define the genes essential to proliferation and survival - discounting false results and even stumbling on previously unknown genes.
The data trawling revealed clusters of genes resistant to a large number of anti-cancer drugs, as well as new gene targets against the most virulent form of the disease - triple negative breast cancer. These include EFNB3 and EPHA4 which have turned up in brain tumour studies, Map Kinase proteins that play an essential role in the cell cycle, and interleukin 32 which is involved in inflammatory pathways. Alongside additional targets, the results also identity new potentially effective drug combinations for treatment of different subtypes
"Very few patients today get a whole genome sequence analysis done on their cancer cells, and the few that do typically receive little medical benefit from the results. The ultimate goal of researchers worldwide is to finally understand each cancer cell's wiring diagram well enough to clarify both the molecular targets against which therapeutics should be developed and the patient groups most likely to respond to any treatment"
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