Targeted Drug Therapy in Non-Small Cell Lung Cancer: Clinical Significance and Possible Solutions-Part I.

Introduction Non-small cell lung cancer (NSCLC) comprises of 84% of all lung cancer cases. NSCLC is usually detected at the advanced or metastatic stage. The treatment option available at this stage is chemotherapy and radiotherapy. Chemotherapy involves conventional non-specific chemotherapeutics, and targeted-protein/receptor specific small molecule inhibitors. Biological targeted therapies such as an antibody-based immunotherapy have also been approved in combination with conventional therapeutics. Approved targeted chemotherapy are directed against the kinase domains of mutated cellular receptors such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinases (ALK), neurotrophic receptor kinases (NTRK) and against downstream signalling molecules such as BRAF (v-raf murine sarcoma viral oncogene homolog B1). There are several other receptors that are mutated/amplified in NSCLC and their inhibitors are currently in clinical trials. Biologically targeted therapy which is approved involves the use of anti-angiogenesis antibodies and antibodies against immune check points. Clinical trials involving similar biological agents with different targets are also underway. Areas covered The rationale for the employment of targeted therapeutics (small molecule inhibitors and biologics) and the resistance that may develop to therapy are discussed. Novel targeted therapeutics in clinical trials, are also included. Expert opinion Molecular and histological profiling of a given tumour specimen to determine the aberrant oncodriver is a must before deciding a targeted therapeutic regimen for the patient. Periodic monitoring of the patients response to a given therapeutic regimen is also mandatory so that any semblance to resistance to therapy can be deciphered and the regimen may be accordingly altered.