Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC).

Background: NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors.

Methods: The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue.

Cancer cell adaptation to chemotherapy.

Background: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors.

Chemosensitization of solid tumor cells by alteration of their susceptibility to apoptosis.

Chemosensitization strategies use the administration of one drug or agent to render cancer cells more susceptible to a second agent. Usually this involves enhanced drug metabolism, improvement of drug uptake or blockage of resistance mechanisms. Alteration of the susceptibility of cancer cells to apoptosis, the process of individual cell death by which many chemotherapeutic drugs act, shows particular promise for therapy in the future, and is the focus of this review.

Chemosensitization of solid tumors by modulation of resistance mechanisms.

The number of drugs available for chemotherapy is growing exponentially, and this trend looks set to continue. Chemosensitization strategies use the administration of one drug or agent to render cancer cells more susceptible to a second agent. Modulation of resistance mechanisms due to xenobiotic membrane pumps such as the multidrug resistant proteins, MDR1/P-glycoprotein or MRP is feasible and a number of new agents have been produced to inhibit drug efflux resulting from expression of these molecules.