Conjugation of proapoptotic peptides with folate and cyanine dyes for enhanced potency and selectivity towards tumor cell lines

Despite continuous advances, anticancer therapy still faces several technical hurdles such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, cyanine dyes and folate to target the mitochondria of tumor cells. Hence, a series of proapoptotic peptides and their conjugates with a cyanine dye and/or a folate were prepared via solid-phase peptide synthesis (SPPS) and their activity tested in different mammalian cell lines. Compounds bearing either a cyanine dye or folate were found to be more cytotoxic than the parent peptides or more selective towards cells overexpressing the folate receptor α, which is commonly found on the surface of tumor cells. Nevertheless, constructs containing both components showed diminished potency and selectivity.

Targeting ALK in Cancer: Therapeutic Potential of Proapoptotic Peptides

ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more. This makes ALK an attractive target for cancer therapy. Since ALK–driven tumors are dependent for their proliferation on the constitutively activated ALK kinase, a number of tyrosine kinase inhibitors have been developed to block tumor growth. While some inhibitors are under investigation in clinical trials, others are now approved for treatment, notably in ALK-positive lung cancer. Their efficacy is remarkable, however limited in time, as the tumors escape and become resistant to the treatment through different mechanisms. Hence, there is a pressing need to target ALK-dependent tumors by other therapeutic strategies, and possibly use them in combination with kinase inhibitors. In this review we will focus on the therapeutic potential of proapoptotic ALK-derived peptides based on the dependence receptor properties of ALK. We will also try to make a non-exhaustive list of several alternative treatments targeting ALK-dependent and independent signaling pathways.