Impact of biomarkers on non-small cell lung cancer treatment

Abstract

Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects and spare toxicities in patients who are unlikely to benefit from treatment. Low excision repair cross-complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) levels have been associated with increased sensitivity to cisplatin and gemcitabine, respectively, while reduced class III beta-tubulin expression has been associated with taxane activity. Initial prospective studies showed the feasibility of a customized approach based on biomarker assessment, and phase III trials will hopefully provide further validation of this approach. The impact of biomarkers for patient selection has now been well established for tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), with EGFR mutations emerging as the most reliable predictor for improved outcome. Relevant clinical issues are represented by the identification of patients who can be reasonably excluded from treatment and by the development of therapeutic approaches able to overcome acquired resistance to anti-EGFR strategies.

Excision repair cross complementation group 1 is a chemotherapy-tolerating gene in cisplatin-based treatment for non-small cell lung cancer

“…This is because ~55% of patients present with advanced stage at time of diagnosis (4). Platinumbased chemotherapy, is currently the mainstay of the advanced NSCLC treatment (5).…”

“…They are heavy metal complexes, and present their therapeutic cytotoxic properties by covalently binding to DNA to form intra-and interstrand cross-links which interfere with normal DNA replication and transcription (8,9). Without efficient DNA repair, the platinum-induced DNA damage eventually leads to cell apoptosis (5). Although the platinum containing agents greatly increase the effectiveness of NSCLC treatment compared with other drugs, platinum-based chemotherapy has apparently reached a therapeutic plateau with limited response to treatment as well as little improvement of survival for patients (10,11), due to the tumors rapidly developing acquired drug resistance which has not yet been overcome (12).…”

PIM1 kinase inhibitors induce radiosensitization in non-small cell lung cancer cells

“…Although such findings have contributed to limited information of the mechanism underlying cellular radioresistance, there are presently no molecular targeted therapies that can be effectively combined with radiation for treating lung cancer. Thus, the identification of biomarker(s) responsible for conferring radioresistance and modification of the irradiation response by radiosensitizers would greatly advance the discovery of drugs that enhance the sensitivity of NSCLC cells to radiation [8][9][10].…”

Intraoperative radiotherapy (IORT) – alternative treatment in functionally nonresectable nonsmall cell lung cancer (NSCLC)

“…Chemotherapy alone enables only one out of three patients therapeutic benefit, therefore massive efforts are carried out to identify biomarkers that might help to choose appropriate drugs [17].…”