From dominance to decline: can we reverse the trend in small molecule and TKI cancer therapies?

Over the past two decades, precision oncology has seen unprecedented advances, particularly with the rise of small molecule drugs. These drugs have significantly benefitted cancer patients with somatic genomic alterations, contributing to precision cancer medicine. Despite their early promise, there is a growing concern that major pharmaceutical companies are recently moving away from developing small molecules and tyrosine kinase inhibitors (TKIs) due to market saturation, primary and secondary resistance, and economic factors. The Inflation Reduction Act (IRA) further threatens innovation by reducing incentives for small molecule drug development. Additionally, patient access to comprehensive genomic testing remains a significant barrier. To reverse this trend, a multifaceted approach is urgently needed. Embracing cutting-edge technologies, fostering collaborations, and regulatory innovation are essential. Addressing systemic deficiencies, improving patient access, and ensuring ongoing investment in personalized medicine are crucial for realizing the full potential of small molecule oncology drugs and improving patient outcomes. Collaboration among stakeholders is imperative for advancing effective cancer treatments.