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Assessment of targets responsible for resistance/sensitivity of lung cancer cells to treatment

We performed a detailed search for factors responsible for resistance of lung cancer cells to treatment. Detailed investigation revealed that although expression of heat-shock proteins was reported to be important for maintaining of resistance of some tumors, level of Hsp72 does not modulate ionizing radiation-induced death of non-small lung carcinomas (NSCLC). In addition, endogenously released Smac was also insufficient to mediate cell death of human lung carcinoma in response to DNA damage. We showed that apoptosis-inducing factor (AIF) determines the chemoresistance of NSCLC. In addition, PKC412 was able to sensitize NSCLC cells to DNA damage.

Importantly, one of the isoforms of p53 family proteins, p73-alpha, efficiently repressed drug-induced apoptosis in small-cell lung carcinomas. Altogether, these data demonstrate that mechanism(s) of resistance of lung cancer cells differ from many other types of tumors and that resistance to chemo- and radiotherapy may imply both nuclear and cytoplasmic compartments. Potential users of this knowledge are pharmaceutical industries developing DNA damaging sensitizing drugs as well as researches, which analyze chemo- and radio-resistance mechanisms or explore cellular responses to different treatment qualities.

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Division of Toxicology, Karolinska Institutet
Box 210, Nobels vag. 13.
171 77 Stockholm
Sweden
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