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：: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. Mos...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.11.006
更新日期：2020-11-18 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2005.07.002
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abstract：:Higher grade histological transformation of follicular lymphoma (FL) to more aggressive diffuse large B-cell lymphomas (DLBCL) occurs in 10-60% of the cases. Review of the current knowledge of genetic and molecular alterations associated with the higher grade transformation of FCL suggests that the process that leads ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/s1044-579x(03)00015-4
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abstract：:DNA damaging agents (ionizing radiation and chemotherapeutics) are considered as most effective in cancer treatment. However, there is a subpopulation of carcinoma cells within the tumour demonstrating resistance to DNA damaging treatment approaches. It is suggested that limited tumour response to this kind of therapy...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2014.06.002
更新日期：2015-04-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.06.001
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abstract：:What is the clinical significance of the expression by common human carcinomas of the Thomsen-Friedenreich (TF) antigen? Described as a terminal disaccharide which is a precursor of MN blood group antigens, it was discovered as a laboratory curiosity 60 years ago, yet its cancer-association has only been appreciated i...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1991-12-01 00:00:00
abstract：:System approaches in biology have a long history. We focus here on the thinking of Paul A. Weiss and Ludwig von Bertalanffy, who contributed a great deal towards making the system concept operable in biology in the early 20th century. To them, considering whole living systems, which includes their organisation or orde...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2011.05.001
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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
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.02.003
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1990-12-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1992-10-01 00:00:00
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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
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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
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2014.05.001
更新日期：2015-04-01 00:00:00
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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：: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
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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
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.02.005
更新日期：2019-10-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
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更新日期：2012-06-01 00:00:00
abstract：:Cellular immediate-early genes are rapidly and transiently activated when cells are stimulated with many different growth factors. This review examines the function of a short immediate-early gene regulatory sequence, the Serum Response Element (SRE), that is sufficient for this transient transcriptional activation. T...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
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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
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2015.04.001
更新日期：2015-08-01 00:00:00
abstract：:Cancer depends on cell death. It can emerge when cell death is deficient, and it could be treated through cancer-cell-specific induction of cell death. However, our understanding of cell death is still incomplete. While a few classical animal models have helped greatly in this respect, more may be learnt from non-clas...
journal_title：Seminars in cancer biology
pub_type： 社论
doi：10.1016/j.semcancer.2006.11.001
更新日期：2007-04-01 00:00:00
abstract：:The two major breast cancer susceptibility genes, BRCA1 and BRCA2, account for the majority of familial breast-ovarian cancer, but only a modest proportion of breast cancer families without ovarian or male breast cancer. Search for additional breast cancer genes with traditional linkage analysis has so far been unsucc...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2001.0393
更新日期：2001-10-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.01.001
更新日期：2019-02-01 00:00:00
abstract：:Cancer-testis antigens (CTAs) are considered as unique and promising cancer biomarkers and targets for cancer therapy. CTAs are multifunctional protein group with specific expression patterns in normal embryonic and adult cells and various types of cancer cells. CTAs are involved in regulating of the basic cellular pr...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.08.006
更新日期：2018-12-01 00:00:00
