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Cancer Cell Int2026;26(1)April 4, 2026Journal Article

PHI-501, a dual inhibitor of RAF and DDR1/2, overcomes MAPK drug resistance in Melanoma.

Sue Min Kim1,2, Sungmin Cho1,2, Gi-Jun Sung3, Ky-Youb Nam3, JeongHyeok Yoon3, Taebo Sim4,5,6,7, Joong Bae Ahn2,8, Sang Joon Shin9,10
1Department of Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
2Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
3Pharos iBio Co., Ltd, Anyang-si, South Korea.
4Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
5Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
6Graduate School of Clinical Drug Discovery & Development, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
7Clinical Candidate Discovery & Development Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
8Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
9Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. SSJ338@yuhs.ac.
10Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. SSJ338@yuhs.ac.
PubMed PMC DOI PDF

Abstract

BACKGROUND: Melanoma, an aggressive skin cancer caused by BRAF or NRAS mutations, is characterized by the hyperactivation of the MAPK pathway. Despite the initial clinical success of RAF and MEK inhibitors in BRAF V600E-mutant melanoma, resistance mechanisms, including MAPK pathway reactivation, compromise their efficacy. This study investigated PHI-501, a next-generation pan-RAF/DDR dual inhibito…

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