Precision Targeting in Cancer: Novel Molecule Mechanisms and Therapeutics

Over the past two decades, the success of kinase inhibitors, such as imatinib and Osimertinib, has demonstrated the feasibility of targeting driver genes. However, as clinical experience with these drugs has accumulated, the emergence of drug resistance has become a new challenge in clinical treatment; at the same time, numerous targets historically considered undruggable (such as transcription factors, RAS, and p53) remain unaddressed in clinical therapy. In recent years, breakthroughs in chemical biology and medicinal chemistry have redefined the boundaries of molecule drug development. Molecules with novel mechanisms of action are opening entirely new therapeutic windows, including protein degradation modulators (PROTACs, molecular glues), covalent inhibitors, protein-protein interaction inhibitors, and new chemical entities discovered through artificial intelligence. These molecules not only target hard-to-reach sites with greater selectivity and potency, but also achieve more durable therapeutic effects by modulating the tumor microenvironment or immune responses. This Research Topic aims to bring together cutting-edge research on novel molecular mechanisms of action in precision cancer therapy. It will focus on new strategies that go beyond the traditional concept of enzyme inhibitors, with an emphasis on discovering and validating new targets, designing and optimizing new molecules, and understanding their unique mechanisms of action to overcome drug resistance or modulate the tumor ecosystem. We welcome a wide range of studies, from drug discovery and preclinical validation to in-depth analyses of mechanisms of action.We particularly encourage submissions focused on:• Discovery and optimization of molecule inhibitors targeting protein-protein interaction interfaces.• Elucidation of the target sites and signaling pathway networks of novel molecule compounds using multi-omics (genomics, proteomics, metabolomics) technologies.• Remodeling of the immunosuppressive microenvironment by modulating the functions of tumor-associated macrophages and cancer-associated fibroblasts via molecules.• Design, synthesis, and evaluation of novel protein degradation technologies—such as PROTACs, molecular glues, and CHAMPs—in cancer models.• The use of AI or deep learning algorithms to predict new targets and indications for molecules or to optimize the ADMET properties of lead compounds. Topic editors: Lu-Qi Cao, Shanzhi Wang, Weifeng Hong, Yuhao Xie Source: https://www.frontiersin.org/research-topics/80051/precision-targeting-in-cancer-novel-molecule-mechanisms-and-therapeutics