Age-related genetic abnormalities: the Achilles' heel for customizing therapy in elderly lung cancer patients

Per Med. 2007 Feb;4(1):59-72. doi: 10.2217/17410541.4.1.59.

Abstract

Aging and cancer are closely related, and DNA repair systems, mainly involving the nucleotide excision repair pathway, have an important caretaker function in both processes. More than half of non-small cell lung cancer patients are elderly, and the expression of some genes involved in the mitotic checkpoint, such as BubR1, declines with aging. Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer; if performance status is good, both elderly and younger patients can tolerate this treatment equally well. Customized cisplatin treatment, based on reduction of the nucleotide excision repair pathway function, could be an attractive approach, and the assessment of mitotic checkpoint genes can be used for selecting docetaxel treatment. Epidermal growth factor receptor (EGFR) mutations are particularly frequent in elderly lung cancer patients who are never-smokers and constitute an attractive target for treatment with EGFR tyrosine kinase inhibitors.

Keywords: CHFR; EGFR mutations; ERCC1; elderly; epidermal growth factor receptor; mitotic checkpoint genes; non-small cell lung cancer.