Targeting ephrin receptor A10 with antibody-drug conjugates for breast cancer.

Despite advances in breast cancer therapy, effective treatment options remain a challenge. The Ephrin receptor A10 (EphA10), a receptor tyrosine kinase, has been reported to be overexpressed in several cancers, including breast and ovarian cancers yet absent in the majority of normal cells except for the male testis. This unique expression profile makes EphA10 an ideal therapeutic target for cancers in women. However, effective EphA10-directed therapies have yet to be developed. To investigate the therapeutic potential of targeting EphA10, we evaluated an antibody drug conjugate strategy. For this purpose, chimeric and humanized EphA10 antibodies were generated and conjugated with monomethyl auristatin E (MMAE). The results showed that EphA10-MMAE exhibited strong cytotoxic effects against EphA10-positive breast cancer cells, including those resistant to FDA-approved drugs such as trastuzumab, lapatinib, PARP inhibitors, and cyclin-dependent kinases 4 and 6 inhibitors. Taken together, these findings highlight EphA10-MMAE as a promising therapeutic strategy for breast cancer, with the potential to overcome drug resistance to existing treatments.