scholarly journals Molecular Targeted Therapy for Breast Cancer: A New Frontiers

2017 ◽  
Vol 14 (3) ◽  
pp. 953-959
Author(s):  
Osama Al-Amer ◽  
Atif Abdulwahab Oyouni ◽  
Shalini Saggu

ABSTRACT: Cancer has become a major public health problem worldwide. Researches focus on the new approaches for cancer treatments that involve the specific targets of the cancer disease. Breast cancer is the most frequent type of cancer among women, and it causes approximately 25% of the deaths in women below the age of 35. Multiple environmental and hereditary factors are responsible for breast cancer such as age, family history, postmenopausal obesity, early menarche, late menopause, alcohol consumption, pregnancy and the use of exogenous hormones. Treatment of breast cancer patients relies primarily on surgery followed by radiotherapy and systemic therapy. Several molecules expressed and secreted by breast cancer cells have been identified by their interactions, invasion and metastasis. These molecular interactions appear to maintain the cancer cells’ survival and growth. The improvement in understanding of the molecular basis of breast cancer will provide possible targets for novel therapies. Therefor, this review focuses on the molecular and cellular basis of the breast cancer treatment.

1995 ◽  
Vol 2 (3) ◽  
pp. 107327489500200
Author(s):  
Anne E. Roberge ◽  
John K. Erban

Breast cancer remains a major public health problem. Prospective randomized trials comparing therapies are essential to improve current therapy but, for those women unable or unwilling to participate in clinical trials, treatment plans are needed. Treatment recommendations can be based on available information from individual trials and from a large collaborative overview. This information will be reviewed with treatment recommendations presented for subpopulations of breast cancer patients.


2021 ◽  
Vol 1 (1) ◽  
pp. 6-9
Author(s):  
Mamadou Ndiaye ◽  
Souleymane Dieng ◽  
Jaafar Thiam ◽  
Adja Coumba Diallo ◽  
Doudou Diouf ◽  
...  

INTRODUCTION: In Senegal, breast cancer is the second female cancer and poses a major public health problem. The aim of this work was to assess prognostic factors in the progression of breast cancer in women. PATIENTS AND METHODS: This is a retrospective study carried out over a period of one year from January 1, 2008 to December 31, 2008 on all the women followed for breast cancer in the oncology department at the Joliot Curie Institute. Thus, 288 breast cancer patients were collected. RESULTS: The average age of our patients was 47.32 years. The average parity was 4.9 children per woman. Twenty-two or 7% of patients had a history of cancer. Clinically, the tumor size was classified as T4 in 180 patients, ie 81%. Lymph node involvement in 188 patients (65.2%). The most frequent histological type was invasive ductal carcinoma with 90.3% of cases. A predominance of grades SBRII and SBRIII was observed (respectively 41% and 46%). Hormone receptors (RH) were positive in eight cases (24%). Overexpression of the HER2 gene was found in only four out of 30 patients. The limits of the surgery were specified in 48 patients with invaded margins in seven patients (14.5%). The presence of vascular emboli was noted in 18 patients among the 29 whose research was carried out in 179 patients, ie 62%. At the time of the initial diagnosis, 45 patients or 19.7% of patients presented at least one distant metastasis. The majority of patients were received at an advanced stage (89%, classified between stage III and IV). Only one patient was received at stage I. Overall survival for breast cancer was 72% at 3 years and 30% at 5 years. The 5-year overall survival of patients with localized disease was 85% compared to 5% for patients with advanced stage. CONCLUSION: The prognostic factors are multiple and often pejorative in our patients with a predominance of young women, locally advanced cancers and aggressive biological forms.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1730
Author(s):  
Evodie Peperstraete ◽  
Clément Lecerf ◽  
Jordan Collette ◽  
Constance Vennin ◽  
Ludivine Raby ◽  
...  

Breast cancer is a major public health problem and the leading world cause of women death by cancer. Both the recurrence and mortality of breast cancer are mainly caused by the formation of metastasis. The long non-coding RNA H19, the precursor of miR-675, is involved in breast cancer development. The aim of this work was to determine the implication but, also, the relative contribution of H19 and miR-675 to the enhancement of breast cancer metastatic potential. We showed that both H19 and miR-675 increase the invasive capacities of breast cancer cells in xenografted transgenic zebrafish models. In vitro, H19 and miR-675 enhance the cell migration and invasion, as well as colony formation. H19 seems to induce the epithelial-to-mesenchymal transition (EMT), with a decreased expression of epithelial markers and an increased expression of mesenchymal markers. Interestingly, miR-675 simultaneously increases the expression of both epithelial and mesenchymal markers, suggesting the induction of a hybrid phenotype or mesenchymal-to-epithelial transition (MET). Finally, we demonstrated for the first time that miR-675, like its precursor H19, increases the stemness properties of breast cancer cells. Altogether, our data suggest that H19 and miR-675 could enhance the aggressiveness of breast cancer cells through both common and different mechanisms.


2021 ◽  
Author(s):  
MAAMAR BOUKABCHA

Abstract Purpose Breast cancer is a public health problem. It impact given several, important consequences for reducing this disease. We did this study to know the situation of breast cancer and the development of cancer registry. Methods Epidemiological, statistical and computer tools are used to collect, analysis and process of the data, we used the medical records to know the data information on female breast cancer patients, by collaboration with of Bedje Sisters Public Hospitalise of Chlef (BSPHC) and the Oran Cancer Registry. Results We collected approximately 177 cases of female breast cancer, and approximately 601595 female populations during the year 2016 for Chlef region. The incidence rate is more than 29 cases of female breast cancer patients per 100000 female populations for each year. Female breast cancer patients of Chlef region is a major public health problem according to the 2016 study. Incidence rates this disease are greatly increased between 55 years and 75 years old. Conclusion Prevention, early diagnostic and different care and treatment play an important role in reducing this chronic disease in this region and why not over the worldwide?


2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1119
Author(s):  
Ivonne Nel ◽  
Erik W. Morawetz ◽  
Dimitrij Tschodu ◽  
Josef A. Käs ◽  
Bahriye Aktas

Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3143
Author(s):  
Sergey E. Parfenyev ◽  
Sergey V. Shabelnikov ◽  
Danila Y. Pozdnyakov ◽  
Olga O. Gnedina ◽  
Leonid S. Adonin ◽  
...  

Breast cancer is the most frequently diagnosed malignant neoplasm and the second leading cause of cancer death among women. Epithelial-to-mesenchymal Transition (EMT) plays a critical role in the organism development, providing cell migration and tissue formation. However, its erroneous activation in malignancies can serve as the basis for the dissemination of cancer cells and metastasis. The Zeb1 transcription factor, which regulates the EMT activation, has been shown to play an essential role in malignant transformation. This factor is involved in many signaling pathways that influence a wide range of cellular functions via interacting with many proteins that affect its transcriptional functions. Importantly, the interactome of Zeb1 depends on the cellular context. Here, using the inducible expression of Zeb1 in epithelial breast cancer cells, we identified a substantial list of novel potential Zeb1 interaction partners, including proteins involved in the formation of malignant neoplasms, such as ATP-dependent RNA helicase DDX17and a component of the NURD repressor complex, CTBP2. We confirmed the presence of the selected interactors by immunoblotting with specific antibodies. Further, we demonstrated that co-expression of Zeb1 and CTBP2 in breast cancer patients correlated with the poor survival prognosis, thus signifying the functionality of the Zeb1–CTBP2 interaction.


2012 ◽  
Vol 11 (11) ◽  
pp. 1457-1467 ◽  
Author(s):  
Olesya Chornoguz ◽  
Alexei Gapeev ◽  
Michael C. O'Neill ◽  
Suzanne Ostrand-Rosenberg

The major histocompatibility complex (MHC) class II-associated Invariant chain (Ii) is present in professional antigen presenting cells where it regulates peptide loading onto MHC class II molecules and the peptidome presented to CD4+ T lymphocytes. Because Ii prevents peptide loading in neutral subcellular compartments, we reasoned that Ii− cells may present peptides not presented by Ii+ cells. Based on the hypothesis that patients are tolerant to MHC II-restricted tumor peptides presented by Ii+ cells, but will not be tolerant to novel peptides presented by Ii− cells, we generated MHC II vaccines to activate cancer patients' T cells. The vaccines are Ii− tumor cells expressing syngeneic HLA-DR and the costimulatory molecule CD80. We used liquid chromatography coupled with mass spectrometry to sequence MHC II-restricted peptides from Ii+ and Ii− MCF10 human breast cancer cells transfected with HLA-DR7 or the MHC Class II transactivator CIITA to determine if Ii− cells present novel peptides. Ii expression was induced in the HLA-DR7 transfectants by transfection of Ii, and inhibited in the CIITA transfectants by RNA interference. Peptides were analyzed and binding affinity predicted by artificial neural net analysis. HLA-DR7-restricted peptides from Ii− and Ii+ cells do not differ in size or in subcellular location of their source proteins; however, a subset of HLA-DR7-restricted peptides of Ii− cells are not presented by Ii+ cells, and are derived from source proteins not used by Ii+ cells. Peptides from Ii− cells with the highest predicted HLA-DR7 binding affinity were synthesized, and activated tumor-specific HLA-DR7+ human T cells from healthy donors and breast cancer patients, demonstrating that the MS-identified peptides are bonafide tumor antigens. These results demonstrate that Ii regulates the repertoire of tumor peptides presented by MHC class II+ breast cancer cells and identify novel immunogenic MHC II-restricted peptides that are potential therapeutic reagents for cancer patients.


2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yifan Wang ◽  
Ruocen Liao ◽  
Xingyu Chen ◽  
Xuhua Ying ◽  
Guanping Chen ◽  
...  

Abstract Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanisms of PAR1 in breast cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast cancer cells, and predicts poor prognosis in ER-negative and high-grade breast cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast cancer.


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