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"Targeted therapy" AND breast

Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein Extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
Hui Yao, Guangchun He, Shichao Yan, Chao Chen, Liujiang Song, Thomas J Rosol, Xiyun Deng
Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers, does not express estrogen receptor (ER) or progesterone receptor (PR) and lacks human epidermal growth factor receptor 2 (HER2) overexpression or amplification. These tumors have a more aggressive phenotype and a poorer prognosis due to the high propensity for metastatic progression and absence of specific targeted treatments. Patients with TNBC do not benefit from hormonal or trastuzumab-based targeted therapies because of the loss of target receptors...
September 27, 2016: Oncotarget
Anthony Gonçalves, François Bertucci, Arnaud Guille, Severine Garnier, José Adelaide, Nadine Carbuccia, Oliver Cabaud, Pascal Finetti, Serge Brunelle, Gilles Piana, Jeanne Tomassin-Piana, Maria Paciencia, Eric Lambaudie, Cornel Popovici, Renaud Sabatier, Carole Tarpin, Magali Provansal, Jean-Marc Extra, François Eisinger, Hagay Sobol, Patrice Viens, Marc Lopez, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Max Chaffanet, Daniel Birnbaum
BACKGROUND: Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population. RESULTS: Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%)...
October 18, 2016: Oncotarget
Patricia Elizalde, Rosalia I Cordo Russo, Maria F Chervo, Roxana Schillaci
Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ErbB-2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades which transduce its effects in BC...
October 7, 2016: Endocrine-related Cancer
Tetsushi Kubota, Shinji Kuroda, Toshiaki Morihiro, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
Trastuzumab(Tmab)is a humanized monoclonalantibody that binds to the human epidermalgrowth factor receptor 2 (HER2). It is clinically used for HER2-positive breast and gastric cancers; however, the use of Tmab is restricted to tumors expressing high levels of HER2(accounting for only 20%of tumors), and Tmab cannot be used for tumors resistant to Tmab. Although novel HER2-targeted agents have been developed to treat Tmab-resistant tumors, none of these have shown clinical efficacy in gastric cancer patients...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Schammim Ray Amith, Krista Marie Vincent, Jodi Marie Wilkinson, Lynne Marie Postovit, Larry Fliegel
Mounting evidence supports a major role for the Na(+)/H(+) exchanger NHE1 in cancer progression and metastasis. NHE1 is hyperactive at the onset of oncogenic transformation, resulting in intracellular alkalinization and extracellular microenvironmental acidification. These conditions promote invasion and facilitate metastasis. However, the signal pathways governing the regulation of exchanger activity are still unclear. This is especially important in the aggressively metastatic, triple-negative basal breast cancer subtype...
October 15, 2016: Cellular Signalling
Dimitrios Zardavas, Konstantinos Tryfonidis, Theodora Goulioti, Martine Piccart
INTRODUCTION: The potential of molecular targeted therapy to improve the clinical outcomes of patients with early-stage breast cancer (BC) as adjuvant therapy has been first demonstrated through endocrine treatment. The introduction of HER2 blockade, through the successful clinical development of trastuzumab, changed the natural history of HER2-positive BC subtype. AREAS COVERED: There are ongoing efforts to augment further the use of targeted agents as adjuvant treatment in BC, hoping that early introduction of targeted therapy blocking key oncogenic drivers of micro-residual disease, will significantly improve clinical outcomes...
October 14, 2016: Expert Review of Anticancer Therapy
Priyakshi Kalita-de Croft, Fares Al-Ejeh, Amy E McCart Reed, Jodi M Saunus, Sunil R Lakhani
Our understanding of the natural history of breast cancer has evolved alongside technologies to study its genomic, transcriptomic, proteomic, and metabolomics landscapes. These technologies have helped decipher multiple molecular pathways dysregulated in breast cancer. First-generation 'omics analyses considered each of these dimensions individually, but it is becoming increasingly clear that more holistic, integrative approaches are required to fully understand complex biological systems. The 'omics represent an exciting era of discovery in breast cancer research, although important issues need to be addressed to realize the clinical utility of these data through precision cancer care...
November 2016: Advances in Anatomic Pathology
Morgan Ballard, Florencia Jalikis, Gregor Krings, Rodney A Schmidt, Yunn-Yi Chen, Mara H Rendi, Suzanne M Dintzis, Kristin C Jensen, Robert B West, Richard K Sibley, Megan L Troxell, Kimberly H Allison
The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Armando Orlandi, Carmela Di Dio, Maria Alessandra Calegari, Carlo Barone
Everolimus and exemestane represent a standard treatment for metastatic hormone receptor-positive/HER2-negative advanced breast cancer resistant to aromatase inhibitors. CA 15-3 serum levels detect soluble forms of MUC-1, a transmembrane oncoprotein aberrantly overexpressed in breast cancers. In clinical practice, CA 15-3 may be used to indicate treatment failure in the absence of readily measurable disease during cytotoxic therapy. In the targeted therapy era, it is important to note that the C-terminal subunit of MUC-1 interacts with PI3K/AKT pathway, inducting cell growth...
October 13, 2016: Biomarkers in Medicine
R Viter, K Jekabsons, Z Kalnina, N Poletaev, S H Hsu, U Riekstina
Using photoluminescent ZnO nanorods and carbohydrate marker SSEA-4, a novel cancer cell recognition system was developed. Immobilization of SSEA-4 antibodies (αSSEA-4) on ZnO nanorods was performed in buffer solution (pH = 7.1) over 2 h. The cancer cell line probes were fixed on the glass slide. One hundred microliters of ZnO-αSSEA-4 conjugates were deposited on the cell probe and exposed for 30 min. After washing photoluminescence spectra were recorded. Based on the developed methodology, ZnO-αSSEA-4 probes were tested on patient-derived breast and colorectal carcinoma cells...
October 12, 2016: Nanotechnology
E Vandendriessche, G Van De Putte, R Van Den Broecke, Etm De Jonge
AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective...
December 28, 2015: Facts, Views & Vision in ObGyn
Huiping Shi, Weili Zhang, Qiaoming Zhi, Min Jiang
In the era of new and mostly effective molecular targeted therapies, human epidermal growth factor receptor 2 positive (HER2+) cancers are still intractable diseases. Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor, has greatly improved breast cancer prognosis in recent years after the initial introduction of trastuzumab (Herceptin). However, clinical evidence indicates the existence of both primary unresponsiveness and secondary lapatinib resistance, which leads to the failure of this agent in HER2+ cancer patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jane Date C Hon, Baljit Singh, Aysegul Sahin, Gang Du, Jinhua Wang, Vincent Y Wang, Fang-Ming Deng, David Y Zhang, Marie E Monaco, Peng Lee
Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy...
2016: American Journal of Cancer Research
Ping Zhong, Jian Zhang, Chao Deng, Ru Cheng, Fenghua Meng, Zhiyuan Zhong
Low tolerability and tumor selectivity restricts many potent anticancer drugs including mertansine from wide clinical use. Here, glutathione-activatable hyaluronic acid-SS-mertansine prodrug (HA-SS-DM1) was designed and developed to achieve enhanced tolerability and targeted therapy of CD44+ human breast tumor xenografts. DM1 was readily conjugated to HA using 2-(2-pyridyldithio)-ethylamine as a linker. Notably, HA-SS-DM1 with a high DM1 content of 20 wt.% had a mean size of ~170 nm at concentrations above 0...
October 10, 2016: Biomacromolecules
Yoon Yang Jung, Chang Lim Hyun, Min-Sun Jin, In Ae Park, Yul Ri Chung, Bobae Shim, Kyu Ho Lee, Han Suk Ryu
PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled...
September 2016: Journal of Breast Cancer
Cornelia Liedtke, Hans-Christian Kolberg
Systemic therapy of metastatic breast cancer may include chemotherapy, endocrine therapy, and targeted therapies (e.g., antibody-based approaches). These agents may be employed alone or in combination based on the patient's breast cancer subtype. Therefore, characterization of the disease phenotype is necessary and may include biopsy of the metastatic site. Novel therapeutic approaches include immunologic therapies, PARP inhibitors, PI3K inhibitors, and CDK4/6 inhibitors, which are currently under investigation in clinical trials...
August 2016: Breast Care
T Yu, G Yang, Y Hou, X Tang, C Wu, X-A Wu, L Guo, Q Zhu, H Luo, Y-E Du, S Wen, L Xu, J Yin, G Tu, M Liu
Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs...
October 10, 2016: Oncogene
Ewa M Michalak, Jane E Visvader
Histone methyltransferases (HMTs) catalyze the methylation of lysine and arginine residues on histone tails and non-histone targets. These important post-translational modifications are exquisitely regulated and affect chromatin compaction and transcriptional programs leading to diverse biological outcomes. There is accumulating evidence that genetic alterations of several HMTs impinge on oncogenic or tumor-suppressor functions and influence both cancer initiation and progression. HMTs therefore represent an opportunity for therapeutic targeting in those patients with tumors in which HMTs are dysregulated, to reverse the histone marks and transcriptional programs associated with aggressive tumor behavior...
September 23, 2016: Molecular Oncology
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