New lung cancer diagnoses and deaths have decreased as a result of reduced smoking and advances in early screening and treatment. However, lung cancer remains the leading cause of cancer deaths, accounting for nearly 20% of all cancer deaths. Of all patients diagnosed with lung cancer, only 10% of those diagnosed have a 5-year survival rate of more than 5 years, and more people die from lung cancer than from breast, colon, and prostate cancers combined.
The concept of degradation of pathogenic proteins by proteolytic targeted chimeras (PROTACs) using the endogenous ubiquitin-proteasome system was first proposed and demonstrated in a proof-of-concept study in 2001. Since then, the technology has become a paradigm shift for small molecule drug discovery and has promoted unprecedented innovations in drug development over the past few years.
Recently, an article entitled “PROTAC therapy as a new targeted therapy for lung cancer” was published by researchers from Brown University in the journal Mol Ther. In this review, the researchers focused on the theoretical basis of PROTAC 32 therapy as a new targeted therapy and the development of PROTAC in lung cancer.
Despite recent advances in molecular therapy, lung cancer remains the leading cause of cancer death. At present, patients with lung cancer face significant challenges due to the lack of targeted treatment options and acquired drug resistance. New strategies for drug development, including those that use the intracellular ubiquitin-proteasome system to induce targeted protein degradation, may promote the field of personalized drugs for patients with lung cancer.
Small molecule proteolysis targeting (PROTACs) for chimerism, which is composed of two ligands, has been developed to target many cancer targets by connecting to the target protein and E3 ubiquitin ligase, providing a promising opportunity for advanced lung cancer.
A typical PROTAC molecule consists of two ligands: one binds to the protein of interest (POI), and the other recruits E3 ligase, which is linked by chemical binders.
The poor physical and chemical properties of PROTAC bring challenges to drug development. In the past two decades, lung cancer has been at the forefront of molecular oncology therapy. New preclinical and early clinical development testing of the expanding portfolio of PROTAC candidates will continue to commit to personalized and targeted treatment to improve the prognosis of patients with advanced lung cancer.