Dataset Information

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

ABSTRACT: Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

SUBMITTER: Ding XX

PROVIDER: S-EPMC5589693 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

Ding Xiao-Xiao XX Zhu Qing-Ge QG Zhang Shi-Ming SM Guan Lei L Li Ting T Zhang Lei L Wang Shi-Yang SY Ren Wan-Li WL Chen Xue-Mei XM Zhao Jing J Lin Song S Liu Zhi-Zhen ZZ Bai Yan-Xia YX He Bing B Zhang Hu-Qin HQ

Oncotarget 20170606 33

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strate ...[more]

PMID: 28903454

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Project description:How can biophysical principles help precision medicine identify rare driver mutations? A major tenet of pragmatic approaches to precision oncology and pharmacology is that driver mutations are very frequent. However, frequency is a statistical attribute, not a mechanistic one. Rare mutations can also act through the same mechanism, and as we discuss below, "latent driver" mutations may also follow the same route, with "helper" mutations. Here, we review how biophysics provides mechanistic guidelines that extend precision medicine. We outline principles and strategies, especially focusing on mutations that drive cancer. Biophysics has contributed profoundly to deciphering biological processes. However, driven by data science, precision medicine has skirted some of its major tenets. Data science embodies genomics, tissue- and cell-specific expression levels, making it capable of defining genome- and systems-wide molecular disease signatures. It classifies cancer driver genes/mutations and affected pathways, and its associated protein structural data guide drug discovery. Biophysics complements data science. It considers structures and their heterogeneous ensembles, explains how mutational variants can signal through distinct pathways, and how allo-network drugs can be harnessed. Biophysics clarifies how one mutation-frequent or rare-can affect multiple phenotypic traits by populating conformations that favor interactions with other network modules. It also suggests how to identify such mutations and their signaling consequences. Biophysics offers principles and strategies that can help precision medicine push the boundaries to transform our insight into biological processes and the practice of personalized medicine. By contrast, "phenotypic drug discovery," which capitalizes on physiological cellular conditions and first-in-class drug discovery, may not capture the proper molecular variant. This is because variants of the same protein can express more than one phenotype, and a phenotype can be encoded by several variants.

Dataset Information

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

Publications

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

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