Protein behind drug-resistant tumors identified

Washington, Aug 07 (ANI): Tumors develop resistance because a protein called AXL helps cancer cells to circumvent the effects of ErbB inhibitors, allowing them to grow unchecked, a new study has revealed.

The findings by Doug Lauffenburger, the Ford Professor of Bioengineering, head of MIT's Department of Biological Engineering and an affiliate member of MIT's Koch Institute for Integrative Cancer Research, have suggested that combining drugs that target AXL and ErbB receptors could offer a better way to fight tumors.

ErbBs, a family of epithelial growth factor receptors (EGFRs), are proteins that are often overactive in cancer cells, causing them to grow and divide uncontrollably.

In the new study, Lauffenburger and colleagues set out to identify factors that help tumor cells become resistant to EGFR and other ErbB inhibitors. To do this, they developed a new computer model and applied it to a large dataset called the Cancer Cell Line Encyclopedia, which includes information on about 1,000 human cancer lines and their responses to different drugs.

The researchers created a machine learning program that can sift through the data and look for pairs of overexpressed proteins that make tumor cells resistant to EGFR inhibitors. In this case, they searched for the EGFR protein in combination with every other possible protein in the database, one pair at a time.

Through this analysis, the researchers found that EGFR paired with the AXL receptor appears to be the strongest marker for EGFR inhibitor resistance. They found this pattern across many types of cancer, including lung, breast and pancreatic.

The new study suggested that AXL inhibitors, either alone or in combination with EGFR inhibitors, might be an effective treatment for triple-negative breast cancer.

The study is published in the journal Science Signaling. (ANI)

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