Chemotherapy and Inflammatory Cytokine Signalling in Cancer Cells and the Tumour Microenvironment.

Cancer is the result of a cell's acquisition of a variety of biological capabilities or 'hallmarks' as outlined by Hanahan and Weinberg. These include sustained proliferative signalling, the ability to evade growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and the ability to invade other tissue and metastasize. More recently, the ability to escape immune destruction has been recognized as another important hallmark of tumours.

Inflammatory cytokine production in tumor cells upon chemotherapy drug exposure or upon selection for drug resistance.

Tumor Necrosis Factor alpha (TNF-α) has been shown to be released by tumor cells in response to docetaxel, and lipopolysaccharides (LPS), the latter through activation of toll-like receptor 4 (TLR4). However, it is unclear whether the former involves TLR4 receptor activation through direct binding of the drug to TLR4 at the cell surface. The current study was intended to better understand drug-induced TNF-α production in tumor cells, whether from short-term drug exposure or in cells selected for drug resistance.

Role of Drug Metabolism in the Cytotoxicity and Clinical Efficacy of Anthracyclines.

Many clinical studies involving anti-tumor agents neglect to consider how these agents are metabolized within the host and whether the creation of specific metabolites alters drug therapeutic properties or toxic side effects. However, this is not the case for the anthracycline class of chemotherapy drugs. This review describes the various enzymes involved in the one electron (semi-quinone) or two electron (hydroxylation) reduction of anthracyclines, or in their reductive deglycosidation into deoxyaglycones.