GCRIS

Chemotherapy frequently involves combination treatment protocols to maximize tumor cell killing. Unfortunately these intensive chemotherapeutic regimes, often show disappointing results due to the development of drug resistance and higher nonspecific toxicity on normal tissues. In cancer treatment, it is critically important to minimize toxicity while preserving efficacy. We have previously addressed this issue and proposed a nanoparticle-based combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent for neutralizing antiapoptotic survivin (BIRC5) to potentiate the efficacy of doxorubicin (DOX). Although the particles exhibited strong anticancer effect on the lung carcinoma A549 and the cervical carcinoma HeLa cells, there were lower-level therapeutic outcomes on the colon carcinoma HCT-116, the leukemia Jurkat and the pancreatic carcinoma MIA PaCa-2 cells. Since targeted therapies are one of the key approaches for overcoming drug resistance, tailoring the treatment of cancer cells with distinct characteristics is necessary to improve the therapeutic outcome of cancer therapy and to minimize potential pharmacokinetic interactions of drugs. In the light of this issue, this study examined whether a cascade therapy with low-dose DOX and survivin-targeted tailored nanoparticles is more effective at sensitizing HCT-116, Jurkat and MIA PaCa-2 cancer cells to DOX-chemotherapy than simultaneous combination therapy. The results demonstrated that the sequential therapy with the protocol comprising addition of the nanoparticles after incubation of cells with DOX clearly advanced the therapeutic outcome of related cancer cells, whereas the reverse protocol resulted in a reduction or delay in apoptosis, emphasizing the critical importance of formulating synergistic drug combinations in cancer therapy.

Autophagy is a physiological process in which cellular components are degraded by the lysosomal machinery. Thereby, organelles are recycled and monomers are produced in order to maintain energy production. Current studies indicate autophagy might suppress or augment survival of cancer cells. Therefore, by elucidating the role of autophagy in cancer pathogenesis, novel therapeutic intervention points may be revealed. Leukemia therapy has advanced in recent years; but a definitive cure is still lacking. Since autophagy often is deregulated in this particular type of cancer, it is clear that future findings will have clinical implications. This review will discuss the current knowledge of autophagy in blood cancers. © 2011 Elsevier Ireland Ltd.

Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

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