Abstract：
:Dysfunction of the TP53 (p53) gene occurs in most if not all human malignancies. Two principal mechanisms are responsible for this dysfunction; mutation and downregulation of wild-type p53 mediated by MDM2/MDM4. Because of its almost universal inactivation in malignancy, p53 is a highly attractive target for the development of new anticancer drugs. Although multiple strategies have been investigated for targeting dysfunctional p53 for cancer treatment, only 2 of these have so far yielded compounds for testing in clinical trials. These strategies include the identification of compounds for reactivating the mutant form of p53 back to its wild-type form and compounds for inhibiting the interaction between wild-type p53 and MDM2/MDM4. Currently, multiple p53-MDM2/MDM4 antagonists are undergoing clinical trials, the most advanced being idasanutlin which is currently undergoing testing in a phase III clinical trial in patients with relapsed or refractory acute myeloid leukemia. Two mutant p53-reactivating compounds have progressed to clinical trials, i.e., APR-246 and COTI-2. Although promising data has emerged from the testing of both MDM2/MDM4 inhibitors and mutant p53 reactivating compounds in preclinical models, it is still unclear if these agents have clinical efficacy. However, should any of the compounds currently being evaluated in clinical trials be shown to have efficacy, it is likely to usher in a new era in cancer treatment, especially as p53 dysfunction is so prevalent in human cancers.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Duffy MJ,Synnott NC,O'Grady S,Crown Jdoi
10.1016/j.semcancer.2020.07.005subject
Has Abstractpub_date
2020-07-31 00:00:00eissn
1044-579Xissn
1096-3650pii
S1044-579X(20)30160-7pub_type
杂志文章,评审abstract：:Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman's initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.11.005
更新日期：2019-06-01 00:00:00
abstract：:Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the ab...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.12.022
更新日期：2019-12-28 00:00:00
abstract：:Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. These modifications are quite appealing as targets for preventative care and therapeutics be...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2009.02.007
更新日期：2009-06-01 00:00:00
abstract：:Managing cancer is now one of the biggest concerns of health organizations. Many strategies have been developed in drug discovery pipelines to help rectify this problem and two of the best ones are drug repurposing and computational methods. The combination of these approaches can have immense impact on the course of ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.04.007
更新日期：2020-04-28 00:00:00
abstract：:Amongst the various types of cancer, breast cancer is a highly heterogeneous disease and known as the leading cause of death among women globally. The extensive interdisciplinary investigation in nanotechnology and cancer biomedical research has been evolved over the years for its effective treatment. However, the adv...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.12.016
更新日期：2019-12-20 00:00:00
abstract：:Prostate specific antigen (PSA) is serine protease produced at high concentrations by normal and malignant prostatic epithelium. It is mainly secreted into seminal fluid, where it digests the gel forming after ejaculation. Only minor amounts of PSA leak out into circulation from the normal prostate, but the release of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0086
更新日期：1999-04-01 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：:Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and as...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.03.001
更新日期：2019-02-01 00:00:00
abstract：:The growth regulatory functions of a family of structurally related polypeptides are mediated through the membrane-bound epidermal growth factor receptor molecule. This ligand family includes epidermal growth factor, transforming growth factor-alpha, amphiregulin, and polypeptides encoded by several poxviruses. The st...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1990-08-01 00:00:00
abstract：:As up to a fifth of all cancers worldwide, have now been linked to microbial infections, it is essential to understand the carcinogenic nature of the bacterial/host interaction. This paper reviews the bacterial targeting of mediators of mitochondrial genomic fidelity and of mitochondrial apoptotic pathways, and compar...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.07.003
更新日期：2017-12-01 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：:Histamine is produced from histidine by histidine decarboxylase (HDC) in many cells including normal and malignant lymphocytes. We examined the expression of HDC and the effect of histamine receptor antagonists on the proliferation of a human T cell line, Jurkat and on antigen-driven proliferation of lymphocytes from ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0306
更新日期：2000-02-01 00:00:00
abstract：:Drug repurposing for cancer therapy is currently a hot topic of research. Theoretically, in contrast to the known hurdles of developing new molecular entities, the approach of repurposing has several advantages. Mostly, it is said that it is faster, safer, easier, and cheaper. In the real world, however, there are onl...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.12.012
更新日期：2019-12-23 00:00:00
abstract：:The need for more effective cancer therapies is omnipresent as the ever-complex, and highly adaptive, mechanisms of tumor biology allow this disease to elude even the most stringent treatment options. The expanding field of proteoglycan signaling is enticing as a reservoir of potential drug targets and prospects for n...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.05.003
更新日期：2020-05-01 00:00:00
abstract：:Glioblastoma (GBM) is an aggressive and incurable brain tumor; its malignancy has been associated with the activity of tumor infiltrating myeloid cells. Myeloid cells play important roles in the tumor control by the immune response, but also in tumor progression. Indeed, GBM exploits multiple mechanisms to recruit and...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.05.014
更新日期：2020-08-01 00:00:00
abstract：:In vitro transformation of replicating myogenic cells by a variety of oncogenes is always accompanied by inhibition of the transition to the terminally differentiated state. Three main levels of interference by oncogenes may ultimately prevent transcription of skeletal muscle-specific genes. First, the transcription o...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:Breast cancer is the most common cancer in women worldwide. There have been many advancements in the treatment of breast cancer leading to an increased population of patients living with this disease. Accumulating evidence suggests that cancer diagnosis and aftermath experienced stress could not only affect the qualit...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.08.011
更新日期：2020-09-03 00:00:00
abstract：:Drug repurposing is a strategy that aims to develop novel cancer treatments through the reuse of existing medicines developed in other disease areas. Such a strategy includes the identification of candidate drugs, clinical development, drug licensing, reimbursement and clinical implementation. This review outlines a l...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.01.008
更新日期：2020-01-23 00:00:00
abstract：:Nutrigenomics effects have an important role in the manipulation of dietary components for human benefit, particularly in cancer prevention or treatment. The impact of dietary components, including phytochemicals, is largely studied by nutrigenomics, looking at the gene expression and molecular mechanisms interacting ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.06.011
更新日期：2017-10-01 00:00:00
abstract：:Macroautophagy (herein autophagy) is an intracellular pathway in which cytoplasmic components are captured by double-membrane vesicles (autophagosomes) that eventually fuse with lysosomes to degrade the cargo. Basal levels of autophagy in all eukaryotic cells maintain cellular homeostasis and under conditions of stres...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.02.015
更新日期：2020-11-01 00:00:00
abstract：:The major cause of death from cancer is due to metastases that are resistant to conventional therapies. Several reasons account for the failure to treat metastases. First, neoplasms are biologically heterogeneous and contain subpopulations of cells with different angiogenic, invasive, and metastatic properties. Second...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2001.0416
更新日期：2002-04-01 00:00:00
abstract：:T cells of the adaptive immune system monitor protein degradation products via their presentation on major histocompatibility complex (MHC) molecules to recognize infected cells. Both macroautophagy and endocytosis target intra- and extracellular constituents, respectively, for lysosomal degradation. This results in a...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.03.005
更新日期：2020-11-01 00:00:00
abstract：:Nasopharyngeal carcinoma (NPC) has a striking geographical and ethnical distribution. It occurs with high frequency in southern China and Southeast Asia. Family clustering was also observed in NPC and a typical family with 15 NPC cases was introduced in this paper. Epidemiological and genetic studies have been carried...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/s1044579x02000871
更新日期：2002-12-01 00:00:00
abstract：:More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-s...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.08.026
更新日期：2020-02-01 00:00:00
abstract：:Systemic treatment of renal cell carcinoma has changed dramatically since 2007, with the development and approval of six new agents, which target complex molecular pathways regulating tumour angiogenesis and cell proliferation and survival. These treatments have significantly improved survival times in metastatic rena...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2012.06.004
更新日期：2013-02-01 00:00:00
abstract：:Neutrophils in the tumor host may promote tumor progression by enhancing angiogenesis, invasion and metastasis. Granulocytic myeloid-derived suppressor cells (MDSC) share many features with neutrophils. Classically, MDSC are viewed as and defined as immunosuppressive cells. In this article we summarize and critically ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2013.02.007
更新日期：2013-06-01 00:00:00
abstract：:Chronic lymphocytic leukaemia (CLL) is the most common form of lymphoid malignancy in Western countries, accounting for around a quarter of all leukaemias. Evidence from epidemiological and family studies have provided evidence for familial clustering of CLL compatible with inherited genetic predisposition to CLL. Dir...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.08.006
更新日期：2010-12-01 00:00:00
abstract：:The discovery of microRNAs (miRNAs) is one of the major scientific breakthroughs in recent years and has revolutionized the way we look at gene regulation. Although we are still at a very early stage in understanding their impact on immunity, miRNAs are changing the way we think about the development of the immune sys...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2008.01.005
更新日期：2008-04-01 00:00:00
abstract：:Dietary flavonoids and other polyphenols show great potential as cancer chemopreventive agents in cell culture studies. This does not translate well into in vivo activity, because of extensive conjugative metabolism of these compounds in the intestine and liver. This paper presents a review of a flavonoid subclass in ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2007.05.002
更新日期：2007-10-01 00:00:00
abstract：:The study of polyomavirus has benefited immensely from two scientific methodologies, cell culture and in vitro studies on one side and the use of transgenic mice as experimental models on the other. Both approaches allowed us to identify cellular products targeted by the viruses, the consequences of these interactions...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2009.02.002
更新日期：2009-08-01 00:00:00
