Role of Platelets in Adaptive Changes to Anti-Angiogenesis Therapy

While anti-angiogenesis therapies have shown remarkable activity in ovarian and other cancers, adaptive resistance can develop within weeks to months. Moreover, concerns have been raised about the potential for more aggressive tumor growth following withdrawal of anti-angiogenesis drugs. Here, we will discuss the role of platelets, specifically platelet extravasation into the tumor microenvironment in stimulating tumor growth. Among the various factors regulating this process, focal adhesion kinase (FAK) expression in platelets plays an important role in their migration into the tumor microenvironment. Mice with FAK-deficient platelets do not exhibit rebound tumor growth following exposure to anti-angiogenesis drugs. Combination therapy with a FAK inhibitor and anti-angiogenic agents reduced tumor growth and inhibited the negative effects following withdrawal of anti-angiogenic therapy. These biological findings, other emerging mechanisms and clinical implications will be discussed.