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Targeted therapy in breast cancer

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https://www.readbyqxmd.com/read/27913999/the-role-of-her2-egfr-and-other-receptor-tyrosine-kinases-in-breast-cancer
#1
Jennifer L Hsu, Mien-Chie Hung
Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the USA will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913998/immunotherapy-for-breast-cancer-past-present-and-future
#2
Alison Spellman, Shou-Ching Tang
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27911711/diaphanous-related-formin-1-as-a-target-for-tumor-therapy
#3
REVIEW
Yuan-Na Lin, Sabine Windhorst
Formins nucleate actin and stabilize microtubules (MTs). Expression of the formin Diaphanous homolog 1 (DIAPH1) is increased in malignant colon carcinoma cells, while expression of DIAPH3 is up-regulated in breast and prostate carcinoma cells. Both DIAPH1 isoforms are required to stabilize interphase MTs of cancer cells, and it has been shown that loss of this function decreases the metastatic potential of these cells. Moreover, depletion of DIAPH3 increases the sensitivity of breast and prostate carcinoma cells to taxanes...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910972/a-liver-microphysiological-system-of-tumor-cell-dormancy-and-inflammatory-responsiveness-is-affected-by-scaffold-properties
#4
A M Clark, S E Wheeler, C L Young, L Stockdale, J Shepard Neiman, W Zhao, D B Stolz, R Venkataramanan, D Lauffenburger, L Griffith, A Wells
Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells...
December 2, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27910741/topotecan-liposomes-a-visit-from-a-molecular-to-a-therapeutic-platform
#5
Shivani Saraf, Ankit Jain, Pooja Hurkat, Sanjay Kumar Jain
Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27909934/current-achievements-and-future-perspectives-of-metronomic-chemotherapy
#6
REVIEW
Adriana Romiti, Rosa Falcone, Michela Roberto, Paolo Marchetti
In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated...
December 1, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27906431/overexpression-of-microrna-365-inhibits-breast-cancer-cell-growth-and-chemo-resistance-through-galnt4
#7
J Zhang, Z Zhang, Q Wang, X-J Xing, Y Zhao
OBJECTIVE: A role of microRNA-365 (miR-365) in the carcinogenesis of breast cancer remains undetermined. In the current study, we addressed this question. PATIENTS AND METHODS: We examined the levels of miR-365 in breast cancer tissue, compared to the paired adjacent non-tumor breast tissue from the patients. We also examined the effects of miR-365 modification on the breast cancer growth and sensitivity to Fluorouracil, as well as the underlying mechanisms. RESULTS: The miR-365 levels in breast cancer tissue were significantly lower than those in control normal breast tissues...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#8
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905893/computational-prediction-of-multidisciplinary-team-decision-making-for-adjuvant-breast-cancer-drug-therapies-a-machine-learning-approach
#9
Frank P Y Lin, Adrian Pokorny, Christina Teng, Rachel Dear, Richard J Epstein
BACKGROUND: Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. METHODS: We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations...
December 1, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27904779/generation-characterization-and-maintenance-of-trastuzumab-resistant-her2-breast-cancer-cell-lines
#10
Sandra Zazo, Paula González-Alonso, Ester Martín-Aparicio, Cristina Chamizo, Ion Cristóbal, Oriol Arpí, Ana Rovira, Joan Albanell, Pilar Eroles, Ana Lluch, Juan Madoz-Gúrpide, Federico Rojo
Trastuzumab became the therapy of choice for patients with HER2-positive breast cancer in 1998, and it has provided clinical benefit ever since. However, a significant percentage of patients show primary resistance to trastuzumab at diagnosis, and most patients with metastatic disease that initially respond to trastuzumab eventually progress (acquired resistance). Consequently, there is an urgent need to improve our knowledge of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903969/targeting-tissue-factor-as-a-novel-therapeutic-oncotarget-for-eradication-of-cancer-stem-cells-isolated-from-tumor-cell-lines-tumor-xenografts-and-patients-of-breast-lung-and-ovarian-cancer
#11
Zhiwei Hu, Jie Xu, Jijun Cheng, Elizabeth McMichael, Lianbo Yu, William E Carson Iii
Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903863/internalization-of-secreted-antigen-targeted-antibodies-by-the-neonatal-fc-receptor-for-precision-imaging-of-the-androgen-receptor-axis
#12
Daniel L J Thorek, Philip A Watson, Sang-Gyu Lee, Anson T Ku, Stylianos Bournazos, Katharina Braun, Kwanghee Kim, Kjell Sjöström, Michael G Doran, Urpo Lamminmäki, Elmer Santos, Darren Veach, Mesruh Turkekul, Emily Casey, Jason S Lewis, Diane S Abou, Marise R H van Voss, Peter T Scardino, Sven-Erik Strand, Mary L Alpaugh, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903634/distinct-receptor-tyrosine-kinase-subsets-mediate-anti-her2-drug-resistance-in-breast-cancer
#13
Peter B Alexander, Rui Chen, Chang Gong, Lifeng Yuan, Jeff S Jasper, Yi Ding, Geoffrey J Markowitz, Pengyuan Yang, Xin Xu, Donald P McDonnell, Erwei Song, Xiao-Fan Wang
Targeted inhibitors of the human epidermal growth factor receptor 2 (HER2) such as trastuzumab and lapatinib are among the first examples of molecularly targeted cancer therapy and have proven largely effective for the treatment of HER2-positive breast cancers. However, approximately half of those patients either do not respond to these therapies or develop secondary resistance. Although a few signaling pathways have been implicated, a comprehensive understanding of mechanisms underlying HER2 inhibitor drug resistance is still lacking...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903149/obesity-and-breast-cancer-prognosis-evidence-challenges-and-opportunities
#14
Sao Jiralerspong, Pamela J Goodwin
Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27902972/unravelling-site-specific-breast-cancer-metastasis-a-microrna-expression-profiling-study
#15
Willemijne A M E Schrijver, Paul J van Diest, Dutch Distant Breast Cancer Metastases Consortium, Cathy B Moelans
Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling.To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902967/the-non-receptor-tyrosine-kinase-tnk2-ack1-is-a-novel-therapeutic-target-in-triple-negative-breast-cancer
#16
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Dhanashree S Kelkar, Mustafa A Bharbuiya, Pamela L Rojas, Vered Stearns, Edward Gabrielson, Pavani Malla, Saraswati Sukumar, Nupam P Mahajan, Akhilesh Pandey
Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers do not express estrogen receptor, progesterone receptor or HER2 receptor and hence are collectively classified as triple negative breast cancer (TNBC). These tumors are often relatively aggressive when compared to other types of breast cancer, and this issue is compounded by the lack of effective targeted therapy. In our previous phosphoproteomic profiling effort, we identified the non-receptor tyrosine kinase TNK2 as activated in a majority of aggressive TNBC cell lines...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#17
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#18
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#19
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899970/fish-testing-of-her2-immunohistochemistry-1-invasive-breast-cancer-with-unfavorable-characteristics
#20
Stella Petroni, Lucia Caldarola, Rachele Scamarcio, Francesco Giotta, Agnese Latorre, Anita Mangia, Giovanni Simone
Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2-positive tumors could benefit from HER2-targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+...
November 2016: Oncology Letters
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