BMAL1 expression is tied to important cellular processes, including cell proliferation, migration, cell cycle and DNA damage repairing. There is increasing evidence that it regulates the expression of various oncogenes and tumor-suppressor genes in cancer cells. Researchers hypothesized that modulating BMAL1 expression could be a new therapeutic approach for treating cancer, such as triple-negative breast cancer (TNBC).
Telomir Pharmaceuticals Inc. has submitted an IND application to the U.S. FDA for its lead candidate, Telomir-1 (Telomir-Zn), for the treatment of advanced and metastatic triple-negative breast cancer (TNBC). Telomir-1 is a first-in-class metal-modulating epigenetic agent designed to restore transcriptional control in tumor cells by targeting intracellular iron-zinc homeostasis.
HORMA domain-containing protein 1 (HORMAD1) is a protein that promotes meiotic recombination and its expression is usually restricted to germ-line cells, although it has been shown to be actively expressed out of context in about 60% of triple-negative breast cancers (TNBCs). A team at The Institute of Cancer Research has found that this aberrant expression in tumor cells perturbs mitotic arrest and generates aneuploidy, leading to a weakening of the spindle assembly checkpoint and in kinetochore-microtubule error correction.
CSN5, a key COP9 signalosome subunit, regulates protein stability in the cell cycle, apoptosis and DNA repair. Its overexpression in cancer promotes tumor growth, metastasis and therapy resistance, making it a potential therapeutic target.
Triple-negative breast cancer (TNBC) cells depend on the transcriptional kinases CDK12 and CDK13 to maintain DNA damage response gene expression and manage replication stress. Due to their functional overlap, inhibition of a single kinase may permit compensatory activity.
Effective targeted therapies against aggressive breast cancer subtypes, such as triple-negative breast cancer (TNBC), are still lacking. Developing therapeutics targeting nonenzymatic, intracellular proteins with causal roles in TNBC progression remains a significant challenge.
Kazia Therapeutics Ltd. has announced promising preclinical and translational data supporting the development of NDL-2, a protein degrader targeting a newly identified mechanism of immunotherapy resistance and metastatic progression.
Recent evidence has suggested threonine tyrosine kinase (TTK) as a crucial element of the mitotic checkpoint for the correct functioning of spindle assembly checkpoint (SAC), making it a potential therapeutic target in cancer.
