Targeting the weak point of cancer by induction of necroptosis

Targeting the weak point of cancers, especially the apoptotic/drug resistant cancers, is critical for the success of cancer chemotherapy. We found that the drug-resistant cancer cell lines overexpressing P-gp, MRP1, BCRP, Bcl-2 and Bcl-xL are susceptible to shikonin, a necroptotic inducer, despite the fact that they are highly resistant to a variety of anticancer agents such as anthracycline antibiotics, vinca alkaloids, taxanes, epipoclophylotoxins, etc. These findings reveal that, although apoptotic/drug resistance is a formidable stronghold of cancer against chemotherapy, necroptotic susceptibility is an intrinsic weak point of cancer. Therefore, targeting the weakness of cancer by induction of necroptosis may have significant potential in cancer chemotherapy, especially in the apoptotic/drug resistant cancers.