In silico discovery and validation of potent small molecule inhibitors targeting the activation function-2 site of human estrogen receptor-¿
Conclusion:
We identified VPC-16230 as an ERα AF2 specific inhibitor that demonstrated promising anti-proliferative effect in breast cancer cell lines including TamR cells. VPC-16230 reduced the expression of ERα-inducible genes including CDC2, which is involved in cell division. We anticipate that the application of ERα AF2 inhibitors will provide a novel approach that can act as complementary therapeutics to treat ERα-positive tamoxifen-resistant and metastatic breast cancers. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 25, 2015 Category: Cancer & Oncology Authors: Kriti SinghRavi MunugantiEric LeblancYu LinEuphemia LeungNada LallousMiriam ButlerArtem CherkasovPaul Rennie Source Type: research
Genetic depletion and pharmacological targeting of ¿v integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models
Conclusion:
These findings show that αv integrin is required for efficient TGF-β/Smad signaling and TGF-β-induced breast cancer cell migration, and for maintaining a mesenchymal phenotype of the breast cancer cells. Our results also provide evidence that targeting αv integrin could be an effective therapeutic approach for treatment of breast cancer tumors and/or metastases that overexpress αv integrin. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 25, 2015 Category: Cancer & Oncology Authors: Yihao LiYvette DrabschPhilippe PujuguetJiang RenTheo van LaarLong ZhangHans van DamPhilippe Clément-LacroixPeter ten Dijke Source Type: research
Inhibition of iNOS as a novel effective targeted therapy against triple negative breast cancer
Conclusions:
Based on the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 22, 2015 Category: Cancer & Oncology Authors: Sergio Granados-PrincipalYi LiuMaria GuevaraElvin BlancoDong ChoiWei QianTejal PatelAngel RodriguezJoseph CusimanoHeidi WeissHong ZhaoMelissa LandisBhuvanesh DaveSteven GrossJenny Chang Source Type: research
A case-control analysis of oral contraceptive use and breast cancer subtypes in the African American Breast Cancer Epidemiology and Risk Consortium
Conclusions:
Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ER- breast cancer, is needed. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 21, 2015 Category: Cancer & Oncology Authors: Traci BetheaLynn RosenbergChi-Chen HongMelissa TroesterKathryn LunettaElisa BanderaPepper SchedinLaurence KolonelAndrew OlshanChristine AmbrosoneJulie Palmer Source Type: research
Prognostic stromal gene signatures in breast cancer
Conclusions:
Our data indicate that the molecular composition of the immune response in a tumor may be a powerful predictor of cancer prognosis. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 21, 2015 Category: Cancer & Oncology Authors: Sofia WinslowKarin LeanderssonAnders EdsjöChrister Larsson Source Type: research
RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy
We examined the difference in expression of RANK/RANKL between pregnant and non-pregnant patients and their association with clinicopathological features and prognosis. We also evaluated genes and pathways associated with RANK/RANKL expression on primary tumors.
Results:
RANKL but not RANK expression was more prevalent in the pregnant group, both on the tumor and adjacent normal tissue, independent of other clinicopathological factors (both P (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 21, 2015 Category: Cancer & Oncology Authors: Hatem AzimFedro PeccatoriSylvain BrohéeDaniel BranstetterSherene LoiGiuseppe VialeMartine PiccartWilliam DougallGiancarlo PruneriChristos Sotiriou Source Type: research
Mammary gland tumor promotion by chronic administration of IGF1 and the insulin analogue AspB10 in the p53 R270H/+ WAPCre mouse model
A human-relevant mouse model is used to determine the carcinogenic potential of diabetes drugs, finding a link between insulin-like molecules with high mitogenic activity and increased risk of breast cancer development. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 18, 2015 Category: Cancer & Oncology Authors: Bas ter BraakChristine SiezenEwoud SpeksnijderEsmee KoedootHarry van SteegDaniela SalvatoriBob van de WaterJan van der Laan Source Type: research
Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth
Conclusions:
This is the first demonstration that HER3 can be targeted with small molecules by eliminating it from the cell membrane. The novel approach used here led to the discovery that perhexiline ablates HER3 expression, and offers an opportunity to identify HER3 ablation modulators as innovative therapeutics to improve survival in breast cancer patients. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 15, 2015 Category: Cancer & Oncology Authors: Xiu-Rong RenJiangbo WangTakuya OsadaRobert MookMichael MorseLarry BarakHerbert LyerlyWei Chen Source Type: research
Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy
Conclusions:
CDK11 and CK2 expression are individually essential for breast cancer cell survival, including TNBC. These genes serve as promising new targets for therapeutic development in breast cancer. (Source: Breast Cancer Research)
Source: Breast Cancer Research - February 11, 2015 Category: Cancer & Oncology Authors: Betsy KrenGretchen UngerMd AbedinRachel VogelChristine HenzlerKhalil AhmedJaneen Trembley Source Type: research
Patient-derived xenograft models of breast cancer and their predictive power
Despite advances in the treatment of patients with early and metastatic breast cancer, mortality remains high due to intrinsic or acquired resistance to therapy. Increased understanding of the genomic landscape through massively parallel sequencing has revealed somatic mutations common to specific subtypes of breast cancer, provided new prognostic and predictive markers, and highlighted potential therapeutic targets. Evaluating new targets using established cell lines is limited by the inexact correlation between responsiveness observed in cell lines versus that elicited in the patient. Patient-derived xenografts (PDXs) ge...
Source: Breast Cancer Research - February 10, 2015 Category: Cancer & Oncology Authors: James WhittleMichael LewisGeoffrey LindemanJane Visvader Source Type: research
Lobular breast cancer: molecular basis, mouse and cellular models
Infiltrating lobular breast cancer (ILC) is the most common special breast cancer subtype. With mutational or epigenetic inactivation of the cell adhesion molecule E-cadherin (CDH1) being confined almost exclusively to ILC, this tumor entity stands out from all other types of breast cancers. The molecular basis of ILC is linked to loss of E-cadherin, as evidenced by human CDH1 germline mutations and conditional knockout mouse models. A better understanding of ILC beyond the level of descriptive studies depends on physiologically relevant and functional tools. This review provides a detailed overview on ILC models, includin...
Source: Breast Cancer Research - February 8, 2015 Category: Cancer & Oncology Authors: Matthias ChristgenPatrick Derksen Source Type: research
Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
Conclusions:
Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer. (Source: Breast Cancer Research)
Source: Breast Cancer Research - January 31, 2015 Category: Cancer & Oncology Authors: Nirmala Bhoo-PathyPetra PeetersCuno UiterwaalH Bueno-de-MesquitaAwang BulgibaBodil BechKim OvervadAnne TjønnelandAnja OlsenFrançoise Clavel-ChapelonGuy FagherazziFlorence PerquierBirgit TeucherRudolf KaaksMadlen SchützeHeiner BoeingPagona LagiouPhilipp Source Type: research
Invasive lobular carcinoma of the breast: morphology, biomarkers and ¿omics
Invasive lobular carcinoma of the breast is the most common ‘special’ morphological subtype of breast cancer, comprising up to 15% of all cases. Tumours are generally of a good prognostic phenotype, being low histological grade and low mitotic index, hormone receptor positive and HER2, p53 and basal marker negative, and with a generally good response to endocrine therapy. Despite this, clinicians face countless challenges in the diagnosis and long-term management of patients, as they encounter a tumour that can be difficult to detect through screening, elicits a very invasive nature, a propensity for widespread metasta...
Source: Breast Cancer Research - January 30, 2015 Category: Cancer & Oncology Authors: Amy McCart ReedJamie KutasovicSunil LakhaniPeter Simpson Source Type: research
MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer
Conclusion:
This study highlights that acquisition of specific deregulated miRNAs is a newly discovered alternative mechanism developed by AI-resistant breast cancer cells to achieve constitutive activation of the AKT/mTOR pathway and develop AI resistance. It also highlights that miR-125b is a new biomarker of poor prognosis and a candidate therapeutic target of AI-resistant breast cancers. (Source: Breast Cancer Research)
Source: Breast Cancer Research - January 30, 2015 Category: Cancer & Oncology Authors: Paul VilquinCaterina DoniniMarie VilledieuEvelyne GrisardLaura CorboThomas BachelotJulie VendrellPascale Cohen Source Type: research
Markers for the identification of late breast cancer recurrence
Postmenopausal women with early breast cancer are at an ongoing risk of relapse, even after successful surgery and treatment of the primary tumor. The treatment of breast cancer has changed in the past few years because of the discovery of prognostic and predictive biomarkers that allow individualized breast cancer treatment. However, it is still not clear how to identify women that are at high risk of a late recurrence. Clinical parameters are good prognostic markers for early recurrence, but only nodal status and, to a lesser extent, tumor size have proven to be strong prognostic markers for late recurrence. Multi-gene s...
Source: Breast Cancer Research - January 27, 2015 Category: Cancer & Oncology Authors: Ivana SestakJack Cuzick Source Type: research
