Small Molecule Cancer Therapy Targets

For some cancers, small molecules that disrupt, inhibit, or agonize target protein function may be the best therapeutic option. Indeed, many new targeted therapeutics are now approved together with companion diagnostics to identify patient populations most likely to benefit from the new treatment.

Despite the successful emergence of immunotherapy and other biologics to fight cancer, some cancer targets remain elusive, where the only option may require the use of small molecule compounds for effective therapy. Small molecules play a crucial role in cancer therapy, offering targeted and systemic approaches to combat the complexities of cancer at the molecular level. These compounds, typically with low molecular weight, can penetrate cell membranes and interfere with specific signaling pathways or cellular processes involved in cancer development and progression. Because of the limitations of immune-mediated therapeutics, small molecules will continue to be critical for the future of cancer therapies.

A promising application of small molecules in cancer therapy involves targeted therapies, where drugs are designed to selectively inhibit specific molecules or pathways implicated in cancer growth. Tyrosine kinase inhibitors, for instance, interfere with signaling pathways involved in cell proliferation and angiogenesis, exhibiting enhanced precision and reduced systemic toxicity compared to traditional chemotherapy. Furthermore, recent developments in targeted protein degradation molecules such PROTACs, LyTACs, molecular glues and others have opened new possibilities to use the ubiquitin system or other protein degradation systems to remove cancer-driving proteins, both intracellular and membrane bound. This illustration depicts some of the major areas for small molecule therapeutics in cancer, many of which have approved drugs for the indicated targets.

Small Molecule Cancer Therapy Targets Diagram

Despite their potential, challenges persist in the development of small molecule cancer therapies, including drug resistance and the need for personalized treatment strategies. Nevertheless, ongoing research and advancements in drug design using AI or conventional screening are continually expanding the repertoire of small molecules, either as stand-alone or in combinations, offering new avenues for innovative and targeted cancer treatments with improved efficacy and reduced side effects.