The paradoxical activity of BRAF inhibitors: potential use in wound healing

The area of wound healing presents a promising field of interest for clinicians as well as the scientific community. A major concern for physicians is the rising number of elderly people suffering from diabetes, leprosy, tuberculosis and the associated chronic wounds. While traditional therapies target basic wound care, innovative strategies that accelerate wound healing are needed. V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors are anti-cancer drugs used primarily for melanoma. They also exhibit paradoxical activity, a phenomenon characterized by unintended activation of the Mitogen-Activated Protein Kinase (MAPK) signalling pathway leading to skin hyperproliferation. Studies have demonstrated that BRAF inhibitors can be repurposed to accelerate the healing of acute and chronic wounds by exploiting their paradoxical activity. This review evaluates studies on BRAF inhibitors by employing a systematic search strategy using databases such as PubMed, Scopus, Google Scholar, and Web of Science. Articles were screened based on relevance to the paradoxical activity of BRAF inhibitors, their mechanisms, and applications in wound healing. Evidence from in vitro, in vivo, and clinical studies demonstrates that BRAF inhibitors can enhance processes such as epithelialization and angiogenesis, essential for wound repair. This review summarizes the reports on the paradoxical activity of BRAF inhibitors, the predicted mechanisms behind the paradoxical activity, and their potential use in wound healing.