Malignant mesothelioma (MM) is a lethal cancer mainly caused by exposure to asbestos, for which, unfortunately, no current treatment has proven effective, despite the identification of several promising therapeutic targets over the years.
SRC, the first oncogene to be discovered, and other variants collectively termed SRC family kinases (SFKs), are appealing targets for cancer therapy because of their key role in many processes underlying the development and progression of several tumor types, including MM. However, although SFK inhibitors successfully counteracted MM malignant features in preclinical studies, results of early clinical trials were not encouraging.
A review article, recently published in the journal Cancers, provides a thorough analysis of the studies exploring the role of SFKs in MM progression and discusses the main hurdles hampering a successful translation of SFK inhibitors in the clinical setting and possible future directions.
“SFK aberrant activation frequently occurs in MM, in which it associates with advanced and metastatic stages and contributes to the alteration of many molecular pathways underlying MM cell proliferation, survival, and invasion,” says Paola Indovina of the Sbarro Health Research Organization in Philadelphia (www.shro.org), first author of the article. “Consistently, preclinical studies by our group and others showed that SFK inhibitors had antiproliferative effects and caused a decrease in MM cell migration and invasion, both alone and in combination with the chemotherapeutic agents currently used in MM therapy and other molecularly targeted therapeutics.”
“Despite these encouraging preclinical results, for the successful translation of SFK inhibitors into the clinic, it is crucial to define reliable predictive markers and gene signatures for selection of MM patients who are most likely to benefit from these drugs, a thorough understanding of their effects on the complex micro and macroenvironment in more faithful preclinical models, and the design of rational combinatorial regimens” says Antonio Giordano, Director and Founder of the Sbarro Health Research Organization and Professor of Pathological Anatomy at the University of Siena, Italy.
About the Sbarro Health Research Organization
The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org
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