scholarly journals Challenges and future of precision medicine strategies for breast cancer based on a database on drug reactions

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Xiping Zhang ◽  
Hongjian Yang ◽  
Ruiping Zhang
Keyword(s):  
Breast Cancer ◽  
Precision Medicine ◽  
Drug Research ◽  
Molecular Subtype ◽  
Drug Reactions ◽  
Match Rate ◽  
Great Progress ◽  
Future Orientations ◽  
Made In ◽  
Main Strategy

Abstract Breast cancer (BC) is a malignancy with the highest incidence in women. Great progress has been made in research related to traditional precision medicine for BC. However, many reports have suggested that patients with BC have not benefited a lot from such progress. Thus, we analyze traditional precision medicine strategies for BC, sum up their limitations and challenges, and preliminarily propose future orientations of precision medicine strategies based on a database on drug reaction of patients with BC. According to related research, traditional precision medicine strategies for BC, which are based on molecular subtypes, perform pertinent treatments, new drug research and development according to molecular typing results. Nevertheless, these strategies still have some deficiencies. First, there are very few patients with each molecular subtype, the match ratio of drugs is low. Second, these strategies can not solve the problem of poor drug sensitivity resulting from heterogeneity. The main strategy we put forward in the present paper is based on patients’ varying drug reactions. Focusing on treating existing patients and maximizing the utilization of existing drugs, it is expected to not have deficiencies of traditional precision medicine for BC, including low match rate and poor therapeutic efficacy arising from tumor heterogeneity of BC.

scholarly journals Pathogenesis and Potential Therapeutic Targets for Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2978
Author(s):  
Chia-Jung Li ◽  
Yen-Dun Tony Tzeng ◽  
Yi-Han Chiu ◽  
Hung-Yu Lin ◽  
Ming-Feng Hou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Efficiency ◽  
Early Recurrence ◽  
New Developments ◽  
Great Progress ◽  
Low Toxicity ◽  
Made In

Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies.

scholarly journals Progress in Local Treatment of Breast Cancer: A Narrative Review

2020 ◽  
Vol 42 (06) ◽  
pp. 356-364
Author(s):  
Francisco Pimentel Cavalcante ◽  
Eduardo Camargo Millen ◽  
Felipe Pereira Zerwes ◽  
Guilherme Garcia Novita
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Local Treatment ◽  
Surgical Techniques ◽  
Distant Metastases ◽  
Randomized Controlled Clinical Trials ◽  
Systemic Adjuvant Therapy ◽  
Surgical Treatments ◽  
Disease Free ◽  
Made In

AbstractThe present paper reports on the local treatment of breast cancer from a historical perspective. A search for articles written in English was made in the Medline and EMBASE databases, and 40 papers were selected. Over the past 10 years, various randomized, controlled clinical trials on the local treatment of breast cancer indicated that patients with the same molecular subtype may receive different individualized surgical treatments aimed at optimizing systemic adjuvant therapy. With a view to retaining the gains made in disease-free and overall survival, surgical techniques have advanced from radical surgery to conservative mastectomies, thus reducing sequelae, while adjuvant and neoadjuvant therapies have contributed toward controlling the disease, both distant metastases and local recurrence. Current studies evaluate whether future breast cancer therapy may even succeed in eliminating surgery to the breast and axilla altogether.

scholarly journals Biological Subtypes of Triple-Negative Breast Cancer

Breast Care ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Michael Hubalek ◽  
Theresa Czech ◽  
Hannes Müller
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Breast Cancers ◽  
Great Progress ◽  
Her 2 ◽  
Disproportionate Number ◽  
New Treatment ◽  
Routine Clinical Application ◽  
Made In

Triple-negative breast cancers (TNBCs) are defined as tumors that are negative for estrogen, progesterone and HER-2 receptor. At a percentage of 10-20% TNBCs represent a minority in all breast cancers. However, because of the poor prognosis this particular subtype, triple negative disease accounts for a disproportionate number of metastatic cases and breast cancer deaths. Identification of its subtypes is essential for understanding the biological characteristics and clinical behavior of TNBC, as well as for developing personalized treatments. This review will focus on the great progress that has been made in the past few years on identifying new targets in TNBC subtypes and a variety of new treatment options that are on the verge of routine clinical application.

scholarly journals Aberrant Epigenetic Regulation in the Pathogenesis of Systemic Lupus Erythematosus and Its Implication in Precision Medicine

2016 ◽  
Vol 149 (3) ◽  
pp. 141-155 ◽  
Author(s):  
Yi Zhan ◽  
Yu Guo ◽  
Qianjin Lu
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Precision Medicine ◽  
Lupus Erythematosus ◽  
Disease Onset ◽  
Systemic Lupus ◽  
Multiple Gene ◽  
Great Progress ◽  
Personalized Approach ◽  
Pituitary Adrenal Axis ◽  
Made In

Great progress has been made in the last decades in understanding the complex immune dysregulation in systemic lupus erythematosus (SLE), yet the efforts to pursue an effective treatment of SLE proved to be futile. The pathoetiology of SLE involves extremely complicated and multifactorial interaction among various genetic and epigenetic factors. Multiple gene loci predispose to disease susceptibility, and the interaction with epigenetic modifications mediated through sex, hormones, and the hypothalamo-pituitary-adrenal axis complicates susceptibility and manifestations of this disease. Finally, certain environmental and psychological factors probably trigger the disease via epigenetic mechanisms. In this review, we summarize and discuss recent epigenetic studies of SLE and suggest a personalized approach to the dissection of disease onset and therapy or precision medicine. We speculate that in the future, precision medicine based on epigenetic and genetic information could help guide more effective targeted therapeutic intervention.

scholarly journals Recommendations for streamlining precision medicine in breast cancer care in Latin America

2021 ◽  
Author(s):  
Isabel Alvarado‐Cabrero ◽  
Franco Doimi ◽  
Virginia Ortega ◽  
Jurema Telles Oliveira Lima ◽  
Rubén Torres ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Latin America ◽  
Precision Medicine ◽  
Cancer Care ◽  
Breast Cancer Care

scholarly journals Highly metastatic claudin-low mammary cancers can originate from luminal epithelial cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Patrick D. Rädler ◽  
Barbara L. Wehde ◽  
Aleata A. Triplett ◽  
Hridaya Shrestha ◽  
Jonathan H. Shepherd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Ras Signaling ◽  
Preneoplastic Lesions ◽  
Independent Manner ◽  
Oncogenic Ras ◽  
Luminal Epithelial Cells

AbstractClaudin-low breast cancer represents an aggressive molecular subtype that is comprised of mostly triple-negative mammary tumor cells that possess stem cell-like and mesenchymal features. Little is known about the cellular origin and oncogenic drivers that promote claudin-low breast cancer. In this study, we show that persistent oncogenic RAS signaling causes highly metastatic triple-negative mammary tumors in mice. More importantly, the activation of endogenous mutant KRAS and expression of exogenous KRAS specifically in luminal epithelial cells in a continuous and differentiation stage-independent manner induces preneoplastic lesions that evolve into basal-like and claudin-low mammary cancers. Further investigations demonstrate that the continuous signaling of oncogenic RAS, as well as regulators of EMT, play a crucial role in the cellular plasticity and maintenance of the mesenchymal and stem cell characteristics of claudin-low mammary cancer cells.

Cadmium, Selenium and Breast Cancer Risk by Molecular Subtype Among Women from Northern Mexico

2021 ◽  
Author(s):  
Elodia Rojas-Lima ◽  
Stephen J. Rothenberg ◽  
Brenda Gamboa-Loira ◽  
Ángel Mérida-Ortega ◽  
Mariano E. Cebrián ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Molecular Subtype ◽  
Northern Mexico ◽  
Cadmium Selenium

scholarly journals Epigenetic Modulation of SPCA2 Reverses Epithelial to Mesenchymal Transition in Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 259
Author(s):  
Monish Ram Makena ◽  
Myungjun Ko ◽  
Donna Kimberly Dang ◽  
Rajini Rao
Keyword(s):  
Breast Cancer ◽  
Secretory Pathway ◽  
Histone Deacetylase Inhibitors ◽  
Epithelial To Mesenchymal Transition ◽  
Molecular Subtype ◽  
Survival Prognosis ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration ◽  
Canonical Wnt

The secretory pathway Ca2+-ATPase SPCA2 is a tumor suppressor in triple receptor negative breast cancer (TNBC), a highly aggressive molecular subtype that lacks tailored treatment options. Low expression of SPCA2 in TNBC confers poor survival prognosis in patients. Previous work has established that re-introducing SPCA2 to TNBC cells restores basal Ca2+ signaling, represses mesenchymal gene expression, mitigates tumor migration in vitro and metastasis in vivo. In this study, we examined the effect of histone deacetylase inhibitors (HDACi) in TNBC cell lines. We show that the pan-HDACi vorinostat and the class I HDACi romidepsin induce dose-dependent upregulation of SPCA2 transcript with concurrent downregulation of mesenchymal markers and tumor cell migration characteristic of epithelial phenotype. Silencing SPCA2 abolished the ability of HDACi to reverse epithelial to mesenchymal transition (EMT). Independent of ATPase activity, SPCA2 elevated resting Ca2+ levels to activate downstream components of non-canonical Wnt/Ca2+ signaling. HDACi treatment led to SPCA2-dependent phosphorylation of CAMKII and β-catenin, turning Wnt signaling off. We conclude that SPCA2 mediates the efficacy of HDACi in reversing EMT in TNBC by a novel mode of non-canonical Wnt/Ca2+ signaling. Our findings provide incentive for screening epigenetic modulators that exploit Ca2+ signaling pathways to reverse EMT in breast tumors.

scholarly journals Expression of Phosphorylated BRD4 Is Markedly Associated with the Activation Status of the PP2A Pathway and Shows a Strong Prognostic Value in Triple Negative Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1246
Author(s):  
Marta Sanz-Álvarez ◽  
Ion Cristóbal ◽  
Melani Luque ◽  
Andrea Santos ◽  
Sandra Zazo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Molecular Target ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Bet Inhibitors ◽  
Brd4 Inhibition ◽  
Bet Protein

The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels. However, the potential clinical significance of pBRD4, as well as its potential correlation with the PP2A pathway in TNBC, remains to be investigated. Here, we evaluated the expression levels of pBRD4 in a series of 132 TNBC patients. We found high pBRD4 levels in 34.1% of cases (45/132), and this alteration was found to be associated with the development of patient recurrences (p = 0.007). Interestingly, BRD4 hyperphosphorylation predicted significantly shorter overall (p < 0.001) and event-free survival (p < 0.001). Moreover, multivariate analyses were performed to confirm its independent prognostic impact in our cohort. In conclusion, our findings show that BRD4 hyperphosphorylation is an alteration associated with PP2A inhibition that defines a subgroup of TNBC patients with unfavorable prognosis, suggesting the potential clinical and therapeutic usefulness of the PP2A/BRD4 axis as a novel molecular target to overcome resistance to treatments based on BRD4 inhibition.

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