Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1

Objective： Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 （BRCA1） gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 （RRM1） gene overexpression enhances resistance to gemcitabine. To further examine the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer （NSCLC）, we performed this non-randomized phase II clinical trial which tested the hypothesis that customized therapy would confer improved outcome over non-customized therapy. Methods： RNA was isolated from fresh tumor tissue. Patients received chemotherapy regimen based on their BRCA1 and RRM1 mRNA levels： both low-cisplatin plus gemcitabine （GP）; both high-vinorelbine plus cisplatin （NP）; BRCA1 low and RRM1 high-cisplatin plus docetaxel （TP）; BRCA1 high and RRM1 low-vinorelbine plus gemcitabine （GN）. Results： From Dec 2005 to Nov 2008, 94 metastatic and locally advanced NSCLC patients from our institute were enrolled in this study. The median age was 58 years old. Among them, 21 patients received GP, 30 patients received TP and 43 patients received NP chemotherapy. GP group had a higher response rate, and longer median time to progression （TTP） and median overall survival （OS） time than the other 2 groups. The response rates in the GP, TP and NP groups were 42.9%, 36.7% and 27.9%, respectively （P=0.568）. The median TTP was 5.6, 5.0, 4.8 months （P=0.975）, respectively, and the median OS time was 12.5, 11.0, 9.7 months （P=0.808）, respectively. Conclusion： Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with higher response rate and longer TTP and OS time in the GP group. This suggests that BRCA1 and RRM1 mRNA levels could be used as biomarkers in individual therapy in NSCLC.

Targeted therapies for patients with advanced NSCLC harboring wild-type EGFR:what's new and what's enough

Historically,non-small cell lung cancer(NSCLC) is divided into squamous and nonsquamous subtypes based on histologic features.With a growing number of oncogenic drivers being identified in squamous and nonsquamous NSCLC,this malignancy has been recently divided into several distinct subtypes according to the specific molecular alterations.This new paradigm has substantially highlighted the treatment of advanced NSCLC,shifting it from standard chemotherapy according to specific histologic subtypes to targeted therapy according to specific oncogenic drivers.The application of epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs) in NSCLC patients harboring activating EGFR mutations has been a representative model of precise medicine in the treatment of NSCLC.As the role of EGFR-TKIs in routine management of patients with advanced NSCLC has been well established,this review provides an overview of alternative targeted therapy in the treatment of NSCLC,including EGFR-TKIs for patients with wild-type EGFR NSCLC,as well as other targeted agents either clinical available or in early- to late-stage development.

Immunotherapy in non-small cell lung cancer:advancements and challenges

In the past 10 years,immune-checkpoint inhibitors(ICIs),targeting programmed death-1(PD-1)/programmed death-ligand 1(PD-L1)axis,have altered the therapeutic landscape of non-small cell lung cancer(NSCLC)and have resulted in long-term survival benefits in a subset of patients.In this editorial,we focused on recent advancements and challenges of ICIs in patients with NSCLC.