Future oncology
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Sphingolipids have emerged as bioeffector molecules, controlling various aspects of cell growth and proliferation in cancer, which is becoming the deadliest disease in the world. These lipid molecules have also been implicated in the mechanism of action of cancer chemotherapeutics. Ceramide, the central molecule of sphingolipid metabolism, generally mediates antiproliferative responses, such as cell growth inhibition, apoptosis induction, senescence modulation, endoplasmic reticulum stress responses and/or autophagy. ⋯ In addition, ceramide metabolism to generate sphingosine-1-phosphate (S1P) by sphingosine kinases 1 and 2 mediates, with or without the involvement of G-protein-coupled S1P receptor signaling, prosurvival, angiogenesis, metastasis and/or resistance to drug-induced apoptosis. Importantly, recent findings regarding the mechanisms by which sphingolipid metabolism and signaling regulate tumor growth and progression, such as identifying direct intracellular protein targets of sphingolipids, have been key for the development of new chemotherapeutic strategies. Thus, in this article, we will present conclusions of recent studies that describe opposing roles of de novo-generated ceramides by ceramide synthases and/or S1P in the regulation of cancer pathogenesis, as well as the development of sphingolipid-based cancer therapeutics and drug resistance.
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The combination of radiotherapy with chemotherapeutic agents that sensitize tumor cells to ionizing radiation has long been regarded as a promising strategy to enhance cancer therapy. Many chemotherapeutic agents interact with radiation and enhance the cytotoxic or anti-tumor effect of radiation through a number of mechanisms. These include an increase in initial radiation damage, inhibition of cellular repair, cell cycle redistribution, enhancement of apoptosis, counteracting hypoxia and overcoming accelerated repopulation. This article focuses on the role of cell cycle perturbations in the radiosensitivity of cancer cells.
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We conducted a systematic review to estimate efficacy and safety of ixabepilone plus capecitabine compared with capecitabine alone for patients of anthracycline- and/or taxane-resistant metastatic breast cancer. ⋯ Ixabepilone plus capecitabine demonstrated clinical activity with an acceptable safety profile, which seems to be a valid option for patients with anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer.
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A review of the literature demonstrated that clinical evaluation cannot be used to determine 'complete response'. The different classification systems of the histopathologic response grading after neoadjuvant radiochemotherapy of esophageal carcinoma are summarized in this report. ⋯ Incorporating chemotherapy administration does not markedly change the difference in required radiation dose. However, when the tumor does respond, the rate of pCR with increasing dosage of chemoradiotherapy increases more rapidly in AC patients than in SCC patients.