scholarly journals Large-scale in-silico identification of a tumor-specific antigen pool for targeted immunotherapy in triple-negative breast cancer

Oncotarget ◽  
2019 ◽  
Vol 10 (26) ◽  
pp. 2515-2529 ◽  
Author(s):  
Jessica Kaufmann ◽  
Nicolas Wentzensen ◽  
Titus J. Brinker ◽  
Niels Grabe
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Large Scale ◽  
Triple Negative ◽  
Specific Antigen ◽  
In Silico Identification ◽  
Targeted Immunotherapy ◽  
Tumor Specific Antigen

scholarly journals Targeting the Id1-Kif11 Axis in Triple-Negative Breast Cancer Using Combination Therapy

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1295
Author(s):  
Archana P. Thankamony ◽  
Reshma Murali ◽  
Nitheesh Karthikeyan ◽  
Binitha Anu Varghese ◽  
Wee S. Teo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Genomic Analysis ◽  
Aurora Kinase ◽  
Cell Cycle Regulators ◽  
Tumor Models ◽  
Tnbc Subtype

The basic helix-loop-helix (bHLH) transcription factors inhibitor of differentiation 1 (Id1) and inhibitor of differentiation 3 (Id3) (referred to as Id) have an important role in maintaining the cancer stem cell (CSC) phenotype in the triple-negative breast cancer (TNBC) subtype. In this study, we aimed to understand the molecular mechanism underlying Id control of CSC phenotype and exploit it for therapeutic purposes. We used two different TNBC tumor models marked by either Id depletion or Id1 expression in order to identify Id targets using a combinatorial analysis of RNA sequencing and microarray data. Phenotypically, Id protein depletion leads to cell cycle arrest in the G0/G1 phase, which we demonstrate is reversible. In order to understand the molecular underpinning of Id proteins on the cell cycle phenotype, we carried out a large-scale small interfering RNA (siRNA) screen of 61 putative targets identified by using genomic analysis of two Id TNBC tumor models. Kinesin Family Member 11 (Kif11) and Aurora Kinase A (Aurka), which are critical cell cycle regulators, were further validated as Id targets. Interestingly, unlike in Id depletion conditions, Kif11 and Aurka knockdown leads to a G2/M arrest, suggesting a novel Id cell cycle mechanism, which we will explore in further studies. Therapeutic targeting of Kif11 to block the Id1–Kif11 axis was carried out using small molecular inhibitor ispinesib. We finally leveraged our findings to target the Id/Kif11 pathway using the small molecule inhibitor ispinesib in the Id+ CSC results combined with chemotherapy for better response in TNBC subtypes. This work opens up exciting new possibilities of targeting Id targets such as Kif11 in the TNBC subtype, which is currently refractory to chemotherapy. Targeting the Id1–Kif11 molecular pathway in the Id1+ CSCs in combination with chemotherapy and small molecular inhibitor results in more effective debulking of TNBC.

scholarly journals A Review of the Hereditary Component of Triple Negative Breast Cancer: High- and Moderate-Penetrance Breast Cancer Genes, Low-Penetrance Loci, and the Role of Nontraditional Genetic Elements

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Darrell L. Ellsworth ◽  
Clesson E. Turner ◽  
Rachel E. Ellsworth
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Association Studies ◽  
African Ancestry ◽  
Genome Wide Association Studies ◽  
Genetic Elements ◽  
Genome Wide ◽  
Increased Risk

Triple negative breast cancer (TNBC), representing 10-15% of breast tumors diagnosed each year, is a clinically defined subtype of breast cancer associated with poor prognosis. The higher incidence of TNBC in certain populations such as young women and/or women of African ancestry and a unique pathological phenotype shared between TNBC and BRCA1-deficient tumors suggest that TNBC may be inherited through germline mutations. In this article, we describe genes and genetic elements, beyond BRCA1 and BRCA2, which have been associated with increased risk of TNBC. Multigene panel testing has identified high- and moderate-penetrance cancer predisposition genes associated with increased risk for TNBC. Development of large-scale genome-wide SNP assays coupled with genome-wide association studies (GWAS) has led to the discovery of low-penetrance TNBC-associated loci. Next-generation sequencing has identified variants in noncoding RNAs, viral integration sites, and genes in underexplored regions of the human genome that may contribute to the genetic underpinnings of TNBC. Advances in our understanding of the genetics of TNBC are driving improvements in risk assessment and patient management.

Demographic variation of Ki67 and its relation with prognosis in triple-negative breast cancer: A single-center pilot project.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11539-e11539
Author(s):  
Mashrafi Ahmed ◽  
Tahmina Begum
Keyword(s):  
Breast Cancer ◽  
Cancer Registry ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Pilot Project ◽  
Single Center ◽  
Ki 67

e11539 Background: Ki-67 is a proliferation marker expressed during cell cycle. ASCO does not recommend this biomarker to be done routinely in breast cancer. As triple negative breast cancer lacks all the ASCO recommended biomarkers (estrogen, progesterone and HER-2 gene), non-recommended markers may carry significant prognostic value in different demographic population. Methods: A retrospective chart review was conducted on patients who were diagnosed with triple negative breast cancer at Saint Joseph Hospital, Chicago from 2005 to 2010. We analyzed the data for Ki67 value among age group, race, menstrual status, tumor histology, stage, treatment given and outcome of the treatment. The data was obtained from medical record, cancer registry and department of pathology. Results: Only 35 cases were found retrospectively. The mean age was 55.6 year. Nearly 47% were African American, 38% White and rest was other races. Most of the cases (71%) were post-menopausal. The average follow-up was 214 days with nearly 62% patients remained disease free, 21% suffered from relapse but alive and 18% died from relapse. The analysis of data is presented here in tabulated form. Conclusions: In our study, we could not reach to statistical significance mostly due to small size of the population. Being a rare subtype of breast cancer, a single center data analysis is not sufficient. This pilot study will encourage us to go for a large scale study involving multi-center or cancer registry data of the state of Illinois. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text]

scholarly journals In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

2016 ◽  
Vol 15 (8) ◽  
pp. 1823-1833 ◽  
Author(s):  
Javier Pérez-Peña ◽  
Gemma Serrano-Heras ◽  
Juan Carlos Montero ◽  
Verónica Corrales-Sánchez ◽  
Atanasio Pandiella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Triple Negative ◽  
In Silico Analysis ◽  
Breast Cancer Treatment ◽  
Bet Inhibitors ◽  
Silico Analysis ◽  
Selection Of

scholarly journals An In Silico Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients

2021 ◽  
Vol 17 (1) ◽  
pp. 42-52
Author(s):  
Daniel Rodrigues de Bastos ◽  
Mércia Patrícia Ferreira Conceição ◽  
Ana Paula Picaro Michelli ◽  
Jean Michel Rocha Sampaio Leite ◽  
Rafael André da Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Triple Negative ◽  
Prognostic Biomarker ◽  
Breast Cancer Patients

In silico analysis of a multifactorial consensus signature (ConSig) for predicting response to anthracycline (A)-based neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients (pts).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1025-1025 ◽  
Author(s):  
Natalie Heather Turner ◽  
Mattia Forcato ◽  
Simona Nuzzo ◽  
Luca Malorni ◽  
Silvio Bicciato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Triple Negative ◽  
In Silico Analysis ◽  
Silico Analysis

Targeted immunotherapy of triple-negative breast cancer by aptamer-engineered NK cells

Biomaterials ◽  
2021 ◽  
pp. 121259
Author(s):  
Zhenghu Chen ◽  
Zihua Zeng ◽  
Quanyuan Wan ◽  
Xiaohui Liu ◽  
Jianjun Qi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Targeted Immunotherapy

scholarly journals SIK2 Restricts Autophagic Flux To Support Triple-Negative Breast Cancer Survival

2016 ◽  
Vol 36 (24) ◽  
pp. 3048-3057 ◽  
Author(s):  
Kimberly E. Maxfield ◽  
Jennifer Macion ◽  
Hariprasad Vankayalapati ◽  
Angelique W. Whitehurst
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Cancer Survival ◽  
Treatment Options ◽  
Autophagic Flux ◽  
Molecular Heterogeneity ◽  
Loss Of Function

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with multiple, distinct molecular subtypes that exhibit unique transcriptional programs and clinical progression trajectories. Despite knowledge of the molecular heterogeneity of the disease, most patients are limited to generic, indiscriminate treatment options: cytotoxic chemotherapy, surgery, and radiation. To identify new intervention targets in TNBC, we used large-scale, loss-of-function screening to identify molecular vulnerabilities among different oncogenomic backgrounds. This strategy returned salt inducible kinase 2 (SIK2) as essential for TNBC survival. Genetic or pharmacological inhibition of SIK2 leads to increased autophagic flux in both normal-immortalized and tumor-derived cell lines. However, this activity causes cell death selectively in breast cancer cells and is biased toward the claudin-low subtype. Depletion of ATG5, which is essential for autophagic vesicle formation, rescued the loss of viability following SIK2 inhibition. Importantly, we find that SIK2 is essential for TNBC tumor growth in vivo . Taken together, these findings indicate that claudin-low tumor cells rely on SIK2 to restrain maladaptive autophagic activation. Inhibition of SIK2 therefore presents itself as an intervention opportunity to reactivate this tumor suppressor mechanism.

Sign in / Sign up

Export Citation Format

Share Document