- Preclinical results of basroparib in combination therapy have been published in the international journal Biochemical Pharmacology.
- This paper, in collaboration with Dr. Jae-Sung Kim's group at the Korea Institute of Radiological and Medical Sciences, demonstrated that tankyrase inhibitor basroparib combined with MEK inhibitors in KRAS-mutant CRC cell lines not only inhibits tumor regrowth but also overcomes acquired resistance to MEK inhibitors.
- MEK inhibitors are a promising option to target the oncogenic in KRAS-mutated CRC. However, many MEK inhibitors have failed to stop the progression of KRAS-mutated CRC in clinical trials, due to the development of acquired resistance to them.
- In a xenograft animal model, tankyrase inhibitor basroparib sensitizes KRAS-mutant CRC cells to MEK inhibitors, reducing tumor growth. In addition, basroparib effectively overcoming acquired resistance to MEK inhibitors in KRAS-G12V/G12D-mutated CRC, by inhibiting Wnt-mediated cancer stemness.
- In addition, in animal studies that induced acquired resistance to MEK inhibitors, the combination of basroparib and MEK inhibitors demonstrated excellent tumor growth inhibition and high survival rates up to 2 months after discontinuation of the drug.
- This study is significant in that it overcomes the limitations of the anti-cancer effect of tankyrase inhibitors administered alone. It may be a good treatment option for colorectal cancer patients who have acquired resistance to MEK inhibitors. Furthermore, it has shown promise in the area of colorectal cancer, a disease for which there are no excellent therapies.
- ST PHARM is planning to conduct preclinical studies in combination with targeted anti-cancer drugs, chemotherapeutic agents, and immuno-oncology drugs of various mechanisms to establish a strategy for subsequent clinical trials, and is also conducting basic research to expand other indications.
[Link] : https://doi.org/10.1016/j.bcp.2025.116842