Precision medicine based on surgical oncology in the era of genome‐scale analysis and genome editing technology

Abstract

Accumulated evidence suggests that multiple molecular and cellular interactions promote cancer evolution in vivo. Surgical oncology is of growing significance to a comprehensive understanding of the malignant diseases for therapeutic application. We have analyzed more than 1000 clinical samples from surgically resected tissue to identify molecular biomarkers and therapeutic targets for advanced malignancies. Cancer stemness and mitotic instability were then determined as the essential predictors of aggressive phenotype with poor prognosis. Recently, whole genome/exome sequencing showed a mutational landscape underlying phenotype heterogeneity in caners. In addition, integrated genomic, epigenomic, transcriptomic, metabolic, proteomic and phenomic analyses elucidated several molecular subtypes that cluster in liver, pancreatic, biliary, esophageal and gastroenterological cancers. Identification of each molecular subtype is expected to realize the precise medicine targeting subtype‐specific molecules; however, there are obstacle limitations to determine matching druggable targets or synthetic lethal interactions. Current breakthroughs in genome editing technology can provide us with unprecedented opportunity to recapitulate subtype‐specific pathophysiology in vitro and in vivo. Given a great potential, on‐demand editing system can design actionable strategy and revolutionize precision cancer medicine based on surgical oncology.

Newly developing methodologies to investigate health hazards posed by ionizing radiation to human space missions

“…The progresses of molecular medicine are not only restricted to CRC. Similar results have been obtained also in the case of other cancers, like for instance hepatocellular cancer, biliary cancer and pancreatic cancer (Tanaka, 2018). Of course, it should not be forgotten that the research in this subject is still ongoing.…”

Prevalence of autoantibodies against Ras‑like GTPases, RalA, in patients with gastric cancer

“…Ras/phosphoinositide 3-kinase (PI3K)/AKT-associated factors were one of the key molecules involved in the epithelial-to-mesenchymal transition of gastric cancer cells (1). Ras-like GTPases, RalA and RalB, are members of the Ras superfamily of small GTPases.…”

Clinical applications of plasma proteomics and peptidomics: Towards precision medicine

“…Put simply, cancers can be considered to arise from the interaction of internal factors (such as multiple gene alterations, immune conditions and hormones) in concert with environmental factors [236–238]. However, cancer is not a single disease [239], but rather hundreds of illnesses sharing common features which arise during the multistep development of cancer, leading to heterogeneity in vitro and in vivo [240–242]. These characteristics are known as The Hallmarks of Cancer and comprise the acquired capabilities for sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism and avoiding immune destruction [240, 243].…”

“…Put simply, cancers can be considered to arise from the interaction of internal factors (such as multiple gene alterations, immune conditions and hormones) in concert with environmental factors [236][237][238]. However, cancer is not a single disease [239], but rather hundreds of illnesses sharing common features which arise during the multistep development of cancer, leading to heterogeneity in vitro and in vivo [240][241][242] The discovery of immune suppression checkpoints has revolutionized the systemic approach to cancer treatment, and tumor immunotherapy has been one of the most successful methods in the field of cancer therapy in recent years [271]. Immune checkpoint blockers (ICBs), including CTLA-4 inhibitors and PD-1 inhibitors, which block checkpoint proteins from binding with their partner proteins, have been widely used in oncology [272][273][274][275].…”