ABSTRACT
Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.
Subject(s)
Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Neoplastic Stem Cells , PrognosisABSTRACT
Three-dimensional (3D) genomics is an emerging discipline that studies the 3D spatial structure and function of genomes, focusing on the 3D spatial conformation of genome sequences in the nucleus and its biological effects on biological processes such as DNA replication, DNA recombination and gene expression regulation. The invention of chromosome conformation capture (3C) technology speeds up the research on 3D genomics and its related fields. Furthermore, the development of 3C-based technologies, such as the genome-wide chromosome conformation capture (Hi-C) and chromatin interaction analysis using paired-end tag sequencing (ChIA-PET), help scientists get insight into the 3D genomes of various species. Aims of 3D genomics are to reveal the spatial genome organization, chromosomal interaction patterns, mechanisms underlying the transcriptional regulation and formation of biological traits of microorganism, plant, animal. Additionally, the identification of key genes and signaling pathways associated with biological processes and disease via chromosome 3C technology boosts the rapid development of agricultural science, life science and medical science. This paper reviews the research progress of 3D genomics, mainly in the concept of 3D genomics, the development of chromosome 3C technologies and their applications in agricultural science, life science and medical science, specifically in the field of tumor.
Subject(s)
Animals , Cell Nucleus , Chromatin/genetics , Chromosomes/genetics , Genome , GenomicsABSTRACT
Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality in the world. The morbidity and mortality of HCC are increasing every year. Liver cancer is a serious threat to public health in China and the death rate of patients with liver cancer in China is the highest in the world. Beyond surgery, chemotherapy and radiotherapy, immunotherapy is an emerging treatment for cancer, which could control and kill tumor cells by relieving the inhibitory status of immune cells in the tumor microenvironment and activating the immune function of the body. Immune checkpoint inhibitors, adoptive immunotherapy and tumor vaccine are the major treatments of immunotherapy. Compared with traditional therapy methods, immunotherapy could enhance immune function, delay tumor progression, prolong the survival time of patients, and becomes a hotspot in the basic and clinical cancer research. This article reviews the research progress of immunotherapy for liver cancer.
Subject(s)
Humans , Cancer Vaccines , Carcinoma, Hepatocellular , Therapeutics , China , Immunotherapy , Liver Neoplasms , Therapeutics , Tumor MicroenvironmentABSTRACT
Tumor is one of the major diseases threatening human health in the 21st century. Surgical resection, radiotherapy, chemotherapy and targeted therapy are the main clinical treatments for solid tumors. However, these methods are unable to eradicate tumor cells completely, and easily lead to the recurrence and progression of tumor. Tumor immunotherapy is a novel treatment that uses human immune system to control and kill tumor by enhancing or restoring anti-tumor immunity. Tumor immunotherapy has shown to produce long-lasting responses in large numbers of patients, and thereby adoptive immunotherapy and immune checkpoint inhibitors could induce remarkable antigen-specific immune responses. Tumor infiltrating lymphocytes (TILs) are highly heterogeneous lymphocytes existing in tumor tissues and play a crucial role in host antigen-specific tumor immune response. Recent studies show that TILs are closely related to the prognosis of patients during the processes of tumorigenesis and treatment. Adoptive immunotherapy mediated by TILs has displayed favorable curative effect in many solid tumors. This paper reviews the recent progress of TILs in solid tumors.