Abstract：
:Small cell lung cancer (SCLC) is a particular subtype of lung cancer with high mortality. Recent advances in understanding SCLC genomics and breakthroughs of immunotherapy have substantially expanded existing knowledge and treatment modalities. However, challenges associated with SCLC remain enigmatic and elusive. Most of the conventional drug discovery approaches targeting altered signaling pathways in SCLC end up in the 'grave-yard of drug discovery', which mandates exploring novel approaches beyond inhibiting cell signaling pathways. Epigenetic modifications have long been documented as the key contributors to the tumorigenesis of almost all types of cancer, including SCLC. The last decade witnessed an exponential increase in our understanding of epigenetic modifications for SCLC. The present review highlights the central role of epigenetic regulations in acquiring neoplastic phenotype, metastasis, aggressiveness, resistance to chemotherapy, and immunotherapeutic approaches of SCLC. Different types of epigenetic modifications (DNA/histone methylation or acetylation) that can serve as predictive biomarkers for prognostication, treatment stratification, neuroendocrine lineage determination, and development of potential SCLC therapies are also discussed. We also review the utility of epigenetic targets/epidrugs in combination with first-line chemotherapy and immunotherapy that are currently under investigation in preclinical and clinical studies. Altogether, the information presents the inclusive landscape of SCLC epigenetics and epidrugs that will help to improve SCLC outcomes.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Khan P,Siddiqui JA,Maurya SK,Lakshmanan I,Jain M,Ganti AK,Salgia R,Batra SK,Nasser MWdoi
10.1016/j.semcancer.2020.11.006subject
Has Abstractpub_date
2020-11-18 00:00:00eissn
1044-579Xissn
1096-3650pii
S1044-579X(20)30240-6pub_type
杂志文章abstract：:Large-scale sequencing methodologies have helped us identify numerous genomic alterations and we have started to scratch the surface of many new targets for treatment of cancer and the associated predictive biomarkers. TRAIL (TNF-related apoptosis-inducing ligand) is a highly appreciated anti-cancer molecule because o...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.01.007
更新日期：2019-10-01 00:00:00
abstract：:The development of vaccines for melanoma has been accelerated by the identification of melanoma-associated antigens, a better understanding of basic immunologic principles, and the ability to construct complex vectors for immunization. The location and context in which T-cell priming occurs significantly influences th...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2003.09.005
更新日期：2003-12-01 00:00:00
abstract：:While the centrality of aberrant cell proliferation in cancer was widely acknowledged long ago, it is only recently that the control of cell death has been recognized as an important target in carcinogenesis. Various lines of evidence now suggest that p53 is a positive regulator of cell death, and particularly of apop...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-06-01 00:00:00
abstract：:Tumor masses are deprived of oxygen and characterized by enhanced glucose uptake followed by glycolysis. Elevated glucose levels induce non-enzymatic glycosylation or glycation of proteins which leads to accumulation of advanced glycation end products (AGE). These AGE molecules bind to their respective receptors calle...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.05.008
更新日期：2018-04-01 00:00:00
abstract：:Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.006
更新日期：2020-04-01 00:00:00
abstract：:Nucleotide sequence analysis at five distinct loci across the 140, 000 bp genomes of more than 60 KSHV samples from KS and PEL tumors from North America, Africa, the Middle East, Asia and the Pacific revealed that they cluster into four major subtypes (A, B, C and D) that have close associations with the geographic an...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0116
更新日期：1999-06-01 00:00:00
abstract：:The HLA-G gene gives rise to six differently spliced mRNAs. The membrane bound HLA-G1 molecule containing all three extracellular domains presents peptides that follow motif requirements similar to those of classical HLA class I molecules. This isoform is also capable of inhibiting Natural Killer (NK) cells, but is on...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0105
更新日期：1999-02-01 00:00:00
abstract：:Distant metastasis is the major cause for therapeutic failures in clinical oncology. Active immunotherapy of patients with low tumor burden would not only contribute to further reduction of the remaining tumor burden to subclinical levels, but it would also establish a constant state of immunity, i.e. immunological me...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-12-01 00:00:00
abstract：:Breast cancer (BC) cell de-sensitization to Tamoxifen (TAM) or other selective estrogen receptor (ER) modulators (SERM) is a complex process associated with BC heterogeneity and the transformation of ER signalling. The most influential resistance-related mechanisms include modifications in ER expression and gene regul...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.12.004
更新日期：2020-12-07 00:00:00
abstract：:Overt neoplasia is often the result of a chronic disease process encompassing an extended segment of the lifespan of any species. A common pathway in the natural history of the disease is the appearance of focal proliferative lesions that are known to act as precursors for cancer development. It is becoming increasing...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2008.03.019
更新日期：2008-10-01 00:00:00
abstract：:The global burden of breast cancer (BC) is increasing significantly. This trend is caused by several factors such as late diagnosis, limited treatment options for certain BC subtypes, drug resistance which all lead to poor clinical outcomes. Recent research has reported the role of epigenetic alterations in the mechan...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.08.009
更新日期：2020-08-25 00:00:00
abstract：:Different types of RNAs identified thus far represent a diverse group of macromolecules that are involved in the regulation of different biological processes. RNA is generally thought to be localized primarily in the nucleus and cytoplasm; however, some types of RNA have been detected in the extracellular milieu. Thes...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2014.04.010
更新日期：2014-10-01 00:00:00
abstract：:While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.03.004
更新日期：2017-04-01 00:00:00
abstract：:Understanding the molecular and genetic determinants of cancer will provide unique opportunities for developing rational and effective therapies. Malignant cells are frequently resistant to chemotherapy and radiation induced programmed cell death (apoptosis). This resistance can occur by mutations in the tumor suppres...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/s1044-579x(02)00134-7
更新日期：2003-04-01 00:00:00
abstract：:Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, sur...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2016.06.003
更新日期：2016-10-01 00:00:00
abstract：:The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors that play a complex and essential role in the regulation of physiologic cell processes, such as proliferation, differentiation, apoptosis and angiogenesis, and serves to organize the epigenetic landscape of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.002
更新日期：2020-02-01 00:00:00
abstract：:DNA copy number amplifications activate oncogenes and are found in the majority of advanced solid tumors. Cell-lineage specificity and oncogene affinity of DNA amplifications in cancer suggest that properties of precursor stem cells and selection pressure in the tissue micro-environment determine the genomic location ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2006.10.005
更新日期：2007-02-01 00:00:00
abstract：:Altering energy metabolism to meet the uncontrolled proliferation and metastasis has emerged as one of the most significant hallmarks in tumors. However, the detailed molecular mechanisms and regulatory actions underlying have not been fully elucidated. As a family of NAD+ dependent protein modifying enzymes, sirtuins...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.11.003
更新日期：2019-08-01 00:00:00
abstract：:There is sufficient evidence to suggest that tumor growth elicits specific immune responses, including CD8(+) and CD4(+) T cell responses that may delay tumor growth and could potentially be harnessed to eradicate cancer. Nevertheless the frequent outcome of cancer is lethality associated with uncontrolled growth and ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2005.11.006
更新日期：2006-04-01 00:00:00
abstract：:Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Similar to many other malignancies, CRC is a heterogeneous disease, making it a clinical challenge for optimization of treatment modalities in reducing the morbidity and mortality associated with this disease. A more precise under...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.05.002
更新日期：2019-04-01 00:00:00
abstract：:Liver cancer is the fifth most common cancer and the third most common cause of cancer related death in the world. The recent development of new techniques for the investigations of global change in the gene expression, signaling pathways and wide genome binding has provided novel information for the mechanisms underl...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.09.001
更新日期：2011-02-01 00:00:00
abstract：:Cancer cells are exposed to adverse conditions within the tumor microenvironment that challenge cells to adapt and survive. Several of these homeostatic perturbations insults alter the normal function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a conserved...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.01.011
更新日期：2018-06-01 00:00:00
abstract：:The anaphase promoting complex/ cyclosome (APC/C), is an evolutionarily conserved protein complex essential for cellular division due to its role in regulating the mitotic transition from metaphase to anaphase. In this review, we highlight recent work that has shed light on our understanding of the role of APC/C coact...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.03.001
更新日期：2020-12-01 00:00:00
abstract：:Hormone-related cancers may originate in utero. Accumulating evidence is given by animal studies, descriptive epidemiologic data and analytic etiologic studies. Indicators of high levels of endogenous pregnancy hormones, like high birth weight and jaundice in the offspring, are associated with increased risk for breas...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0073
更新日期：1998-08-01 00:00:00
abstract：:Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in res...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1992-04-01 00:00:00
abstract：:Although chemokines and their receptors were initially identified as regulators of cell trafficking during inflammation and immune response, they have emerged as crucial players in all stages of tumor development, primary growth, migration, angiogenesis, and establishment as metastases in distant target organs. Neuroe...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2008.10.009
更新日期：2009-04-01 00:00:00
abstract：:The marginal level of clinical responses to the Chloroethylnitrosoureas (CENU, i.e. BCNU, CCNU, MeCCNU) suggests that there may exist an innate mechanism of resistance in tumors to these chemotherapeutic agents. A decade of research from many laboratories around the world has led to the identification of the mechanism...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1991-08-01 00:00:00
abstract：:Primary liver cancer is the second most common malignancy, and currently results in 360,000 incident cases, and 350,000 deaths a year in China. For the past four decades, three national surveys on cancer mortality during the periods of 1973-1975, 1990-1992, and 2004-2005 have made it possible to estimate China's past ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.11.002
更新日期：2011-02-01 00:00:00
abstract：:Bone marrow transplantation is currently used to treat a variety of life-threatening diseases. Its applications could be expanded if the risks of graft-versus-host disease (GVHD), a complex pathologic disease, could be reduced. Immunotoxins may provide a means to control drug refractory GVHD. This article will discuss...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1996.0009
更新日期：1996-04-01 00:00:00
abstract：:Transfection experiments indicate that a number of genes can induce or suppress the metastatic phenotype. These genes include ten oncogenes, plasminogen activator, and three suppressor genes. The biochemical mechanism(s) whereby each of these genes alters the metastatic phenotype is poorly understood. Hypotheses conce...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1991-04-01 00:00:00
