Combating cancer by inhibiting the protein focal adhesion kinase (FAK) may not be as straight forward as previously thought, a study published in Nature Communications suggests. FAK inhibitors, used at high doses have been shown remarkable efficacy in controlling cancer. However, the work here shows that the biological role of FAK in cancer progression is complex, and partial inhibition of the enzyme could enhance, rather than decrease, tumour growth.
FAK is expressed in most cells of the body and regulates a range of physiological processes, including the formation of new blood vessels - a process known as angiogenesis. Because tumours depend on angiogenesis to ensure nutrient supply for their continued growth, FAK inhibitors are currently being developed as anti-cancer drugs. Vassiliki Kostourou and colleagues engineered mice that produce low levels of FAK and show that tumours in these mice, paradoxically, grow larger and have more new blood vessels than normal mice. The same situation also arises in normal mice treated with low doses of a FAK inhibitor. This demonstrates a contrast to the assumption that FAK inhibition generally slows down tumour growth, which motivates the development of FAK inhibitors as anti-cancer drugs.
The findings suggest that high doses of FAK inhibitors, which ensure complete inhibition of the enzyme, might be required to achieve therapeutic success.
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