Janaki Sharma

The Evolving Role of Biomarkers in Personalized Lung Cancer Therapy

Prior to the last decade, treatment for lung cancer was differentiated only by the main histological groups of small cell lung cancer (SCLC) and NSCLC. However, it is now known that differences in tumor histology affect response to chemotherapy and side effect profiles of certain agents. For example, during early clinical trials of the anti-VEGF monoclonal antibody (mAB) bevacizumab, a phase 2 study of carboplatin and paclitaxel plus or minus bevacizumab showed improved response rate, time to progression and overall survival (OS) with bevacizumab. However, the incidence of life-threatening pulmonary hemorrhage was 30% with squamous histology compared to 4% with adenocarcinoma [3] . Due to this unacceptable risk, further studies excluded squamous histology, and

Emerging treatment for ALK-positive lung cancer

ABSTRACT Introduction: Lung cancer is associated with poor prognosis and limited benefit from chemotherapy. The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of targetable genetic alterations, including the ALK fusion oncogene. Areas covered: Three drugs have been approved for clinical use in ALK-positive patients – crizotinib, ceritinib and alectinib. Unfortunately, treatment resistance inevitably develops. Several mechanisms of acquired resistance are reported. In this review, we will discuss emerging treatment options in ALK-positive advanced NSCLC and strategies to overcome resistance mechanisms, including newer generation of ALK inhibitors, Hsp90 inhibitors and immunotherapy. Expert opinion: Tremendous advances have been made in the treatment of ALK-positive lung cancers, but management hurdles still exist, including universal development of resistance to ALK inhibitors and limited CNS activity. Given that specific treatment strategies target distinct patterns of resistance, re-biopsy at the time of progression appears necessary to optimize management. However, there remain many issues in routine clinical application including the burden placed on the patients by serial biopsies and the risks of repeat invasive procedures. Future studies are needed to validate the usage of non- or minimally invasive tests and to determine the optimal orders of utilizing different ALK inhibitors.