scholarly journals Immune Check-Point Inhibitors in Breast Cancer: Current Evidence and Future Directions

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Mosteiro M ◽  
◽  
Cejuela M ◽  
Pernas S ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Triple Negative ◽  
New Combination ◽  
Current Evidence ◽  
Check Point ◽  
Future Directions ◽  
Combination Strategies ◽  
Check Point Inhibitors

Check-point inhibitors have erupted as a treatment option for numerous kinds of neoplasms. Although there have been some achievements, the evidence supporting their use in breast cancer is scarce. Combinations with chemotherapy seem to provide better outcomes, and triple negative is the subtype most likely to benefit from them. New combination strategies are undergoing research to improve these results. Other approaches to determining biomarkers that identify which populations clearly benefit from these therapies are needed. Here, we review the clinical data of the role of immune check-point inhibitors in early and advanced breast cancer and present emerging strategies.

scholarly journals Role of Immunotherapy in Triple-Negative Breast Cancer

2020 ◽  
Vol 18 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Tanya E. Keenan ◽  
Sara M. Tolaney
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Future Directions ◽  
Call To Action ◽  
Combination Strategies ◽  
Key Characteristics

Immune checkpoint inhibitors (ICIs) have led to durable clinical remissions in many metastatic cancers. However, the single-agent efficacy of ICIs in breast cancer is low, including in triple-negative breast cancer (TNBC), which has several key characteristics that enhance ICI responses. Strategies to improve anticancer immune responses in TNBC are urgently needed to extend survival for patients with metastatic disease. This review presents ICI monotherapy response rates and discusses combination strategies with chemotherapy, targeted therapies, and novel immunotherapies. It concludes with a summary of immunotherapy biomarkers in TNBC and a call to action for future directions of research critical to advancing the efficacy of immunotherapy for patients with TNBC.

scholarly journals The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 529 ◽  
Author(s):  
Benjamin Gordon ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Vaccines ◽  
Molecular Mechanisms ◽  
New Combination ◽  
Breast Carcinomas ◽  
Therapeutic Vaccines ◽  
Combination Strategies ◽  
Disseminated Disease

Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. Cancer immunotherapy has revolutionized the treatment of several cancers, with therapeutic vaccines aiming to direct the cytotoxic immune program against tumor cells showing particular promise. However, these results have yet to translate to breast cancer, which remains largely refractory from such approaches. Recent evidence suggests that the breast tumor microenvironment (TME) is an important and long understudied barrier to the efficacy of therapeutic vaccines. Through an improved understanding of the complex and biologically diverse breast TME, it may be possible to advance new combination strategies to render breast carcinomas sensitive to the effects of therapeutic vaccines. Here, we discuss past and present efforts to advance therapeutic vaccines in the treatment of breast cancer, the molecular mechanisms through which the TME contributes to the failure of such approaches, as well as the potential means through which these can be overcome.

Endocrine resistance in advanced breast cancer: current evidence and future directions

2012 ◽  
Vol 1 (4) ◽  
pp. 305-314 ◽  
Author(s):  
Carlos H Barrios ◽  
André P Fay ◽  
Marcio Debiasi ◽  
Gustavo Werutsky
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Resistance ◽  
Advanced Breast ◽  
Current Evidence ◽  
Future Directions

scholarly journals AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?

2021 ◽  
Vol 12 ◽  
Author(s):  
Federica Martorana ◽  
Gianmarco Motta ◽  
Giuliana Pavone ◽  
Lucia Motta ◽  
Stefania Stella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
New Combination ◽  
Cancer Subtypes ◽  
Combination Strategies

The serine/threonine kinase AKT is a key component of the PI3K/AKT/mTOR signaling pathway as it exerts a pivotal role in cell growth, proliferation, survival, and metabolism. Deregulation of this pathway is a common event in breast cancer including hormone receptor-positive (HR+) disease, HER2-amplified, and triple negative tumors. Hence, targeting AKT represents an attractive treatment option for many breast cancer subtypes, especially those resistant to conventional treatments. Several AKT inhibitors have been recently developed and two ATP-competitive compounds, capivasertib and ipatasertib, have been extensively tested in phase I and II clinical trials either alone, with chemotherapy, or with hormonal agents. Additionally, phase III trials of capivasertib and ipatasertib are already under way in HR+ and triple-negative breast cancer. While the identification of predictive biomarkers of response and resistance to AKT inhibition represents an unmet need, new combination strategies are under investigation aiming to boost the therapeutic efficacy of these drugs. As such, trials combining capivasertib and ipatasertib with CDK4/6 inhibitors, immune checkpoint inhibitors, and PARP inhibitors are currently ongoing. This review summarizes the available evidence on AKT inhibition in breast cancer, reporting both efficacy and toxicity data from clinical trials along with the available translational correlates and then focusing on the potential use of these drugs in new combination strategies.

Role of Carboplatin in the Treatment of Triple Negative Early- Stage Breast Cancer

2015 ◽  
Vol 10 (2) ◽  
pp. 101-110 ◽  
Author(s):  
Matias E. Valsecchi ◽  
Gerrit Kimmey ◽  
Arvinder Bir ◽  
Damian Silbermins
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Early Stage Breast Cancer

scholarly journals 19P A dichotomous oncogenic role of the splicing factor SF3A3 in MYC-driven triple-negative breast cancer

2021 ◽  
Vol 32 ◽  
pp. S28
Author(s):  
A. Bosch ◽  
M. Cieśla ◽  
P. Cao Thi Ngoc ◽  
S. Mutukumar ◽  
G. Honeth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Splicing Factor

scholarly journals The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 462
Author(s):  
Víctor Mayoral-Varo ◽  
María Pilar Sánchez-Bailón ◽  
Annarica Calcabrini ◽  
Marta García-Hernández ◽  
Valerio Frezza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Sh2 Domain ◽  
Model Systems ◽  
System A ◽  
Promising Therapeutic Target ◽  
Relevant Role ◽  
Inactivating Mutation

The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems. These cells conditionally expressed, under tetracycline control (Tet-On system), a c-Src variant with point-inactivating mutation of the SH2 adapter domain (R175L). The expression of this mutant reduced the self-renewal capability of the enriched population of breast cancer stem cells (BCSCs), demonstrating the importance of the SH2 adapter domain of c-Src in the mammary gland carcinogenesis. In addition, the analysis of anchorage-independent growth, proliferation, migration, and invasiveness, all processes associated with tumorigenesis, showed that the SH2 domain of c-Src plays a very relevant role in their regulation. Furthermore, the transfection of two different aptamers directed to SH2-c-Src in both SUM159PT and MDA-MB-231 cells induced inhibition of their proliferation, migration, and invasiveness, strengthening the hypothesis that this domain is highly involved in TNBC tumorigenesis. Therefore, the SH2 domain of c-Src could be a promising therapeutic target and combined treatments with inhibitors of c-Src kinase enzymatic activity may represent a new therapeutic strategy for patients with TNBC, whose prognosis is currently very negative.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

Sign in / Sign up

Export Citation Format

Share Document