Abstract:
:DNA repair deficiencies are common among cancer cells and represent a potential vulnerability that might be exploited by targeting compensatory repair pathways. However, the identification of synthetically lethal combinations of DNA repair defects, although of significant clinical relevance, has been somewhat anecdotal. Although numerous models have been proposed to explain synthetic lethality among DNA repair mutations, we have only a limited understanding of why a given mutation should render cells sensitive to another. In this issue of Cancer Discovery, Dietlein and colleagues define a general connection between mutations in genes involved in homologous recombination and sensitivity to inhibitors of non-homologous end joining. In doing so, they provide a mechanism to demarcate a set of seemingly diverse tumors that may be highly responsive to established DNA repair-targeted therapeutics.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Hemann MTdoi
10.1158/2159-8290.CD-14-0316subject
Has Abstractpub_date
2014-05-01 00:00:00pages
516-8issue
5eissn
2159-8274issn
2159-8290pii
4/5/516journal_volume
4pub_type
相关文献
Cancer Discovery文献大全abstract::Preliminary findings from a recent study suggest that combining intermittent fasting or a fasting-mimicking diet with endocrine therapy for hormone receptor-positive breast cancer may improve treatment efficacy and reduce side effects. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-NB2020-084
更新日期:2020-11-01 00:00:00
abstract::Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor micro...
journal_title:Cancer discovery
pub_type: 杂志文章,评审
doi:10.1158/2159-8290.CD-12-0345
更新日期:2012-10-01 00:00:00
abstract::53BP1 integrates pRB activity with the DNA damage response by binding to methylated K810. ...
journal_title:Cancer discovery
pub_type: 评论,杂志文章
doi:10.1158/2159-8290.CD-RW2014-164
更新日期:2014-09-01 00:00:00
abstract::It is possible to decipher the clonal architecture of a tumor and the sequence in which cancer clones acquire genomic alterations through multiregion sequencing (M-seq). Serial evaluation of tumor specimens through M-seq can provide valuable information on the molecular basis of resistance to therapy. ...
journal_title:Cancer discovery
pub_type: 评论,杂志文章
doi:10.1158/2159-8290.CD-15-0739
更新日期:2015-08-01 00:00:00
abstract::An international team of researchers has uncovered multiple new germline mutations that may influence the development of sarcomas. Notably, they found that variants in several DNA damage sensing and repair genes contribute greatly to sarcoma risk, including BRCA2, ATM, ATR, and ERCC2. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-NB2016-108
更新日期:2016-10-01 00:00:00
abstract::Internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITD) occurs in 30% of poor prognosis acute myeloid leukaemias (AMLs). Limited clinical efficacy of FLT3 inhibitors highlights the need for alternative therapeutic modalities in this subset of disease. Using human and murine models of FLT3-ITD-dri...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-20-0738
更新日期:2021-01-12 00:00:00
abstract::AKT inhibitors have promising activity in AKT1E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinica...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-19-1209
更新日期:2020-04-01 00:00:00
abstract::The NCI and Department of Veterans Affairs (VA) are collaborating on the NCI and VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, which will launch at 12 VA facilities across the country. The program aims to increase participation of veterans with cancer in NCI-sponsored clinical trials. ...
journal_title:Cancer discovery
pub_type: 新闻
doi:10.1158/2159-8290.CD-NB2018-097
更新日期:2018-08-01 00:00:00
abstract::Metabolic reprogramming enables cancer cell growth, proliferation, and survival. This reprogramming is driven by the combined actions of oncogenic alterations in cancer cells and host cell factors acting on cancer cells in the tumor microenvironment. Cancer cell intrinsic mechanisms activate signal transduction compon...
journal_title:Cancer discovery
pub_type: 杂志文章,评审
doi:10.1158/2159-8290.CD-20-1211
更新日期:2021-01-27 00:00:00
abstract::A new mathematical model finds that tumor neoantigen quality trumps quantity when it comes to predicting response to immunotherapy and the likelihood of long-term survival among patients with cancer. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-NB2017-165
更新日期:2018-01-01 00:00:00
abstract::An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The therapy would be the first of its kind approved for cancer and has the potential to transform standard of...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-NB2017-108
更新日期:2017-09-01 00:00:00
abstract:UNLABELLED:Indoleamine 2,3-dioxygenase (IDO) enzyme inhibitors have entered clinical trials for cancer treatment based on preclinical studies, indicating that they can defeat immune escape and broadly enhance other therapeutic modalities. However, clear genetic evidence of the impact of IDO on tumorigenesis in physiolo...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-12-0014
更新日期:2012-08-01 00:00:00
abstract::Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4-CD8-NK1.1- innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infiltrating PDA in mice and human...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-19-0161
更新日期:2019-09-01 00:00:00
abstract::A new compound with anti-leukemia activity perturbs gene transcription by modulating super-enhancer activity. ...
journal_title:Cancer discovery
pub_type: 新闻
doi:10.1158/2159-8290.CD-NB2015-149
更新日期:2015-12-01 00:00:00
abstract::A recent study integrating proteomic and genomic analyses uncovered unexpected similarities in some types of pediatric brain tumors, such as certain craniopharyngiomas and low-grade gliomas, suggesting potential treatments and more refined prognoses. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-NB2020-119
更新日期:2021-01-07 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide with no clinically confirmed oncogenic driver. Although preclinical studies implicate the FGF19 receptor FGFR4 in hepatocarcinogenesis, the dependence of human cancer on FGFR4 has not been demonstrated. Fisogatinib (BLU-554) is a potent an...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-19-0367
更新日期:2019-12-01 00:00:00
abstract::Mutating a conserved motif in the activation loop of MEC1 (ATR) revealed the activation mechanism. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-RW2020-170
更新日期:2020-11-20 00:00:00
abstract::Ceritinib and other second-generation inhibitors have demonstrated promising anticancer activity in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Specifically, they can overcome resistance due to certain gatekeeper mutations acquired following crizotinib exposure. These agents now provi...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-14-0410
更新日期:2014-06-01 00:00:00
abstract:UNLABELLED:Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which control access to an allosteric pocket adjacent to the ATP-binding site, has ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-15-0060
更新日期:2015-06-01 00:00:00
abstract::Although BRAF-MEK inhibition can enhance the immune recognition of melanoma cells, the mechanisms that underlie this remain poorly defined. In this issue of Cancer Discovery, Erkes and colleagues present new data showing that BRAF-MEK inhibition activates pyroptosis in melanoma cells through gasdermin E cleavage, lead...
journal_title:Cancer discovery
pub_type: 评论,杂志文章
doi:10.1158/2159-8290.CD-19-1441
更新日期:2020-02-01 00:00:00
abstract::In the setting of recent exciting clinical results and numerous ongoing trials, Piotrowska and colleagues explore mechanisms of acquired resistance to the mutant-specific EGFR inhibitor rociletinib, and demonstrate that loss of T790M, EGFR amplification, and small-cell transformation are all clinically relevant mechan...
journal_title:Cancer discovery
pub_type: 评论,杂志文章
doi:10.1158/2159-8290.CD-15-0616
更新日期:2015-07-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abunda...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-18-0567
更新日期:2019-03-01 00:00:00
abstract::New research shows immunotherapy can cause lethal inflammation in both young and aged mice that are obese. Restricting calories in aged mice protected them from toxicity, and giving young obese mice a drug for autoimmune disease prevented the fatal reactions. ...
journal_title:Cancer discovery
pub_type: 新闻
doi:10.1158/2159-8290.CD-NB2014-171
更新日期:2015-01-01 00:00:00
abstract::HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant so...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-19-1014
更新日期:2020-05-01 00:00:00
abstract::Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer. Improved progression-free survival was seen regardless of the presence or absence of germline BRCA mutations, or o...
journal_title:Cancer discovery
pub_type:
doi:10.1158/2159-8290.CD-NB2016-137
更新日期:2016-12-01 00:00:00
abstract::Despite recent advances in the use of immunotherapy, only a minority of patients with small cell lung cancer (SCLC) respond to immune checkpoint blockade (ICB). Here, we show that targeting the DNA damage response (DDR) proteins PARP and checkpoint kinase 1 (CHK1) significantly increased protein and surface expression...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-18-1020
更新日期:2019-05-01 00:00:00
abstract::According to survival results from a phase II trial of brentuximab vedotin, 34 patients with relapsed or refractory classic Hodgkin lymphoma had a complete response with this CD30-targeting antibody-drug conjugate; 13 remain in remission 5 years later. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-NB2016-100
更新日期:2016-09-01 00:00:00
abstract::LKB1 inactivation generates a redox imbalance that promotes ADC-to-SCC transdifferentiation in NSCLC. ...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-RW2015-089
更新日期:2015-07-01 00:00:00
abstract:UNLABELLED:CD96 has recently been shown as a negative regulator of mouse natural killer (NK)-cell activity, with Cd96(-/-)mice displaying hyperresponsive NK cells upon immune challenge. In this study, we have demonstrated that blocking CD96 with a monoclonal antibody inhibited experimental metastases in three different...
journal_title:Cancer discovery
pub_type: 杂志文章
doi:10.1158/2159-8290.CD-15-0944
更新日期:2016-04-01 00:00:00
abstract::The FDA granted accelerated approval to selinexor plus low-dose dexamethasone for triple-class refractory multiple myeloma, despite an advisory panel's concerns about the drug's toxicity and the lack of randomized clinical data. ...
journal_title:Cancer discovery
pub_type: 新闻
doi:10.1158/2159-8290.CD-NB2019-085
更新日期:2019-09-01 00:00:00