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Receptor tyrosine kinases (RTKs) are key regulatory signaling proteins governing cancer cell growth and metastasis. During the last two decades, several molecules targeting RTKs were used in oncology as a first or second line therapy in different types of cancer. However, their effectiveness is limited by the appearance of resistance or adverse effects. In this review, we summarize the main features of RTKs and their inhibitors (RTKIs), their current use in oncology, and mechanisms of resistance. We also describe the technological advances of artificial intelligence, chemoproteomics, and microfluidics in elaborating powerful strategies that could be used in providing more efficient and selective small molecules inhibitors of RTKs. Finally, we discuss the interest of therapeutic combination of different RTKIs or with other molecules for personalized treatments, and the challenge for effective combination with less toxic and off-target effects.

Tyrosine Kinase Inhibitors in Cancer: Breakthrough and Challenges of Targeted Therapy