Selective sensitization of tumors to chemotherapy by marine-derived lipids: a review

Despite great improvements, a significant proportion of cancer patients still die, mainly because of the development of metastases. At this stage, current treatments still rely heavily on conventional chemotherapy for most cancers. The efficacy of chemotherapy is dose-dependent, which is limited by toxicity to non-tumor tissues, as a result of its poor tumor selectivity. To improve survival length and preserve quality of life, the challenge is to develop approaches aimed at increasing chemotherapy toxicity to tumor tissue while not affecting non-tumor tissues. Marine-derived lipids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the potential to differentially sensitize tissues to chemotherapy. These lipids enhance the cytotoxicity of 15 anticancer drugs (antimetabolites, alkylating or intercalating agents, microtubule stabilizers, Abl tyrosine kinase inhibitor and arsenic trioxide) to a variety of cancer cell lines or tumors in animals, used as models for breast, prostate, colonic, lung, cervical, ovarian cancers, neuroblastomas, leukemia or lymphomas. However, DHA and EPA do not sensitize non-tumor tissues to anticancer drugs, which suggests that the effect of these lipids is tumor selective. Two phase II clinical trials already support these results, and randomized, phase III trials are ongoing. In this review, we discuss the double-faceted properties of these lipids, and then focus on their potential for transfer to the patient in the light of current therapeutic strategies. Should their beneficial effects be confirmed, the consequences could be considerable by opening up the prospect of systematic supplementation during cancer treatment, a significant shift in current cancer therapeutic paradigms.