Therapeutics: Importin 7 (IPO7); MAP kinase 1 (MAPK1; ERK-2); MAPK3 (ERK-1)
In vitro and mouse studies suggest a peptide inhibitor of IPO7 binding to MAPK1 or MAPK3 could help treat cancer. In multiple human cancer cell lines, a cell-penetrating peptide derived from MAPK1 and MAPK3 decreased binding of IPO7 to MAPK1 or MAPK3 and decreased cell proliferation compared with a scrambled peptide. In human melanoma cell lines, the peptide also increased apoptosis. In mice with melanoma, breast or colon cancer xenografts, the peptide decreased growth compared with vehicle, and in mice with melanoma xenografts, it decreased tumor recurrence compared with vemurafenib. Next steps include identifying a small molecule that inhibits IPO7 binding to MAPK1 or MAPK3.
Daiichi Sankyo Co. Ltd., Roche and Chugai Pharmaceutical Co. Ltd. market Zelboraf vemurafenib, an oral small molecule inhibitor of oncogenic BRAF V600E, to treat melanoma and have the compound in Phase II testing to treat thyroid cancer. ...