Biomarkers of DNA repair and related pathways: significance in non-small cell lung cancer.
OBJECTIVE
To review selected biomarkers of DNA repair and related pathways as they relate to the management of patients with non-small cell lung cancer (NSCLC), emphasizing the role of individualized, chemotherapy for advanced disease, and discussing potential applications in early disease.


RESULTS
The activity of molecular-targeted agents in NSCLC patients whose tumor possesses relevant biomarkers [such as epidermal growth factor receptor (EGFR) activating mutations and ALK translocations] has made personalized therapy possible. In addition, preclinical and clinical studies have shown that histopathological and biomolecular factors can correlate with clinical outcome in patients with NSCLC treated with chemotherapy. As a result, tumor histology is now routinely considered in selecting chemotherapy for NSCLC patients, such as pemetrexed for nonsquamous histology. Molecular tumor and host factors, including genes involved in DNA-repair and synthesis, are potentially even more relevant as predictive biomarkers of tumor response to chemotherapy. However, individual molecular markers and gene signatures need further validation and standardization, before routine use in the clinic can be recommended.


CONCLUSIONS
In the era of molecular-targeted agents, individualized therapy based on molecular biomarkers has become a reality in the treatment of patients with advanced NSCLC. Further studies are needed to optimize current treatment algorithms with regard to biomarkers for chemotherapy benefit, to refine molecular markers, and to translate these findings to early stage NSCLC.
Department of Medical Oncology and Clinical Research, University Hospital Bern, Bern, Switzerland.
Sacha I
SI
Rothschild
Oliver
O
Gautschi
Primo N
PN
Lara
Philip C
PC
Mack
David R
DR
Gandara
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*
D014408:Biomarkers, Tumor