Integration of Next-generation Sequencing and Immune Checkpoint Inhibitors in Targeted Symptom Control and Palliative Care in Solid Tumor Malignancies: A Multidisciplinary Clinician Perspective

Abstract

The molecular characterization of solid tumor malignancies with respect to tumorgenesis, risk stratification, and prognostication of chemotherapeutic side effects is multi-faceted. Characterizing these mechanisms requires a detailed understanding of cytogenetics and pharmacology. In addition to the standard palliative care interventions that address issues such as fatigue, neuropathy, performance status, depression, nutrition, cachexia, anxiety, and medical ethics, we must also delve into individual chemotherapy side effects. Comprehending these symptoms is more complex with the advent of broader targeted therapies. With the advent and initiation of Foundation Medicine (FMI) testing, we have been able to tailor regimens to the individual genetics of the patient. Next-generation sequencing (NGS) is a bioinformatic analysis used in order to create a targeted effort to understand the complex genetics of a vast array of malignancies. Through the process known as high-throughput sequencing we, as clinicians, can obtain more real-time genetic data and incorporate the information into our reasoning process. The process involves a broad manner in which deoxyribonucleic acid (DNA) sequence data is obtained including genome sequencing and resequencing, protein-DNA or proteinomics, chromatin immunoprecipitation (ChIP)-sequencing, ribonucleic acid (RNA) sequencing, and epigenomic analysis. High-throughput sequencing techniques including single molecule real-time sequencing, ion semiconductor sequencing, pyrose sequencing, sequencing by synthesis, sequencing by ligation, nanopore sequencing, and chain termination (otherwise known as Sanger sequencing) have expanded the realm of NGS and clinicians options.

Keywords: braf; kras; metastatic colorectal cancer; next generation sequencing; nras; palliative; pd-1 inhibitor; symptom control; targeted therapy; uveal melanoma.