What is the role of genetics in resistance to platinum-based chemotherapy for the treatment of non–small cell lung cancer (NSCLC)?

Updated: Jul 15, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Answer

Although platinum-based chemotherapy is currently standard of care in NSCLC, data suggest that certain individual tumors may have inherent resistance to platinum compounds. Excision repair cross-complementation group 1 (ERCC1) is one such genetic abnormality, and high levels of ERCC1 messenger RNA in tumor tissue have been associated with resistance to platinum.

Holm et al found that, in patients receiving carboplatin and gemcitabine for inoperable NSCLC, the expression of ERCC1 had different effects on survival in men and women. In a retrospective study in 163 patients, men whose tumors were ERCC1 negative survived significantly longer than men with ERCC1 -positive tumors (median survival, 11.8 mo vs 7.9 mo). Conversely, ERCC1 status had no effect on survival in women. [121]

As with ERCC1, increased expression of ribonucleotide reductase subunit 1 (RRM1) has been associated with decreased response to gemcitabine and platinum.

In the future, therapy for NSCLC may need to be tailored on the basis of the genetic characteristics of individual tumors. Gene expression profiling has been studied for accurate classification of NSCLC histology as well as prognostication, but this remains experimental.


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