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Targeted therapy in breast cancer

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https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#1
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777274/the-natural-agent-4-vinylphenol-targets-metastasis-and-stemness-features-in-breast-cancer-stem-like-cells
#2
Hoi-Wing Leung, Chun-Hay Ko, Grace Gar-Lee Yue, Ingrid Herr, Clara Bik-San Lau
BACKGROUND AND PURPOSE: Cancer stem-like cells (CSC) are regarded as the source of tumour origins, metastasis and drug resistance, and limits current treatment regimens. Previously, we reported the first study of the anti-angiogenic and anti-tumour activities of 4-vinylphenol. To further examine the therapeutic role of 4-vinylphenol, the inhibitory effects of 4-vinylphenol on cancer stemness, drug resistance and metastasis in breast cancer were investigated in the present study. STUDY DESIGN AND METHODS: We enriched parental MDA-MB-231 cells with CSCs in serum-free medium to give spheroids...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29777007/development-of-64-cu-nota-trastuzumab-for-her2-targeting-radiopharmaceutical-with-improved-pharmacokinetics-for-human-study
#3
Sang-Keun Woo, Su Jin Jang, Min-Jung Seo, Ju Hui Park, Byoung Soo Kim, Eun Jung Kim, Yong Jin Lee, Tae Sup Lee, Gwang Il An, In Ho Song, Youngho Seo, Kwang Il Kim, Joo Hyun Kang
Purpose The purpose of this study was to develop 64 Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2. Methods Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64 Cu. Serum stability and immunoreactivity of 64 Cu-NOTA-trastuzumab were tested. Small animal PET imaging and biodistribution study were performed in HER2-positive breast cancer xenograft model (BT-474). Internal dosimetry of experimental animals was performed using the image-based approach with the Monte Carlo N-Particle Code...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776011/predicting-nonadherence-to-adjuvant-endocrine-therapy-in-women-with-early-stage-breast-cancer
#4
Arden L Corter, Reuben Broom, David Porter, Vernon Harvey, Michael Findlay
BACKGROUND: Failing to take endocrine therapy (ET) as prescribed (nonadherence) increases risk of morbidity and mortality from breast cancer recurrence. We explored predictors of nonadherence, including demographic, clinical, treatment and personal factors, among women newly prescribed ET for early stage breast cancer. We also examined predictors of their thoughts about stopping treatment (TST). METHODS: A baseline survey prior to ET assessed demographics, illness beliefs, beliefs about medicines, fear of recurrence, symptoms and negative affect...
May 18, 2018: Psycho-oncology
https://www.readbyqxmd.com/read/29775610/monocarboxylate-transporters-in-breast-cancer-and-adipose-tissue-are-novel-biomarkers-and-potential-therapeutic-targets
#5
Zhiyu Li, Qi Wu, Si Sun, Juan Wu, Juanjuan Li, Yimin Zhang, Changhua Wang, Jingping Yuan, Shengrong Sun
Monocarboxylate transporters (MCTs) are transmembrane proteins that control the lactate metabolism and associated with poor prognosis in solid tumors including breast cancer (BC). This study aimed to evaluate the clinical and prognostic value of MCTs used by immunohistochemistry and quantum dots-based fluorescent imaging technique in BC and surrounding stroma with emphasis on the interaction between tumour and stroma. Moreover, the data from The Cancer Genome Atlas (TCGA) was analyzed to evaluate the association between MCTs mRNA expression and prognosis of breast cancer patients...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775157/blood-based-biomarkers-in-breast-cancer-from-proteins-to-circulating-tumor-cells-to-circulating-tumor-dna
#6
Michael J Duffy, Enda W McDermott, John Crown
Biomarkers are the key to personalized treatment in patients with breast cancer. While tissue biomarkers are most useful in determining prognosis and upfront predicting response to therapy, circulating protein biomarkers such as CA 15-3 and carcinoembryonic antigen are mainly used in monitoring response to endocrine or chemotherapy in patients with advanced disease. Although several centers measure biomarkers in asymptomatic patients following curative surgery for primary breast cancer, the clinical utility of this practice is unclear...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29774083/engineered-microfluidic-bioreactor-for-examining-the-three-dimensional-breast-tumor-microenvironment
#7
Matthew Rogers, Tammy Sobolik, David K Schaffer, Philip C Samson, Andrew C Johnson, Philip Owens, Simona G Codreanu, Stacy D Sherrod, John A McLean, John P Wikswo, Ann Richmond
The interaction of cancer cells with the stromal cells and matrix in the tumor microenvironment plays a key role in progression to metastasis. A better understanding of the mechanisms underlying these interactions would aid in developing new therapeutic approaches to inhibit this progression. Here, we describe the fabrication of a simple microfluidic bioreactor capable of recapitulating the three-dimensional breast tumor microenvironment. Cancer cell spheroids, fibroblasts, and endothelial cells co-cultured in this device create a robust microenvironment suitable for studying in real time the migration of cancer cells along matrix structures laid down by fibroblasts within the 3D tumor microenvironment...
May 2018: Biomicrofluidics
https://www.readbyqxmd.com/read/29774078/targeting-intracellular-mmps-efficiently-inhibits-tumor-metastasis-and-angiogenesis
#8
Yaqi Lv, Xiangmei Zhao, Lidan Zhu, Sijia Li, Qingqing Xiao, Wei He, Lifang Yin
Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs. Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra...
2018: Theranostics
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#9
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29774068/platelet-camouflaged-nanococktail-simultaneous-inhibition-of-drug-resistant-tumor-growth-and-metastasis-via-a-cancer-cells-and-tumor-vasculature-dual-targeting-strategy
#10
Lijia Jing, Haijing Qu, Dongqi Wu, Chaojian Zhu, Yongbo Yang, Xing Jin, Jian Zheng, Xiangsheng Shi, Xiufeng Yan, Yang Wang
Multidrug resistance (MDR) poses a great challenge to cancer therapy. It is difficult to inhibit the growth of MDR cancer due to its chemoresistance. Furthermore, MDR cancers are more likely to metastasize, causing a high mortality among cancer patients. In this study, a nanomedicine RGD-NPVs@MNPs/DOX was developed by encapsulating melanin nanoparticles (MNPs) and doxorubicin (DOX) inside RGD peptide (c(RGDyC))-modified nanoscale platelet vesicles (RGD-NPVs) to efficiently inhibit the growth and metastasis of drug-resistant tumors via a cancer cells and tumor vasculature dual-targeting strategy...
2018: Theranostics
https://www.readbyqxmd.com/read/29773994/biological-roles-of-aberrantly-expressed-glycosphingolipids-and-related-enzymes-in-human-cancer-development-and-progression
#11
REVIEW
Dinghao Zhuo, Xiang Li, Feng Guan
Glycosphingolipids (GSLs), which consist of a hydrophobic ceramide backbone and a hydrophilic carbohydrate residue, are an important type of glycolipid expressed in surface membranes of all animal cells. GSLs play essential roles in maintenance of plasma membrane stability, in regulation of numerous cellular processes (including adhesion, proliferation, apoptosis, and recognition), and in modulation of signal transduction pathways. GSLs have traditionally been classified as ganglio-series, lacto-series, or globo-series on the basis of their diverse types of oligosaccharide chains...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29772881/geographic-access-to-radiation-therapy-facilities-and-disparities-of-early-stage-breast-cancer-treatment
#12
Yan Lin, Michael C Wimberly, Patricia Da Rosa, Joseph Hoover, William F Athas
Few studies of breast cancer treatment have focused on the Northern Plains of the United States, an area with a high mastectomy rate. This study examined the association between geographic access to radiation therapy facilities and receipt of breast cancer treatments among early-stage breast cancer patients in South Dakota. Based on 4,209 early-stage breast cancer patients diagnosed between 2001 and 2012 in South Dakota, the study measured geographic proximity to radiation therapy facilities using the shortest travel time for patients to the closest radiation therapy facility...
May 7, 2018: Geospatial Health
https://www.readbyqxmd.com/read/29770821/a-size-shrinkable-nanoparticle-based-combined-anti-tumor-and-anti-inflammatory-strategy-for-enhanced-cancer-therapy
#13
Zhengze Lu, Yang Long, Xingli Cun, Xuhui Wang, Jianping Li, Ling Mei, Yiliang Yang, Man Li, Zhirong Zhang, Qin He
Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy...
May 17, 2018: Nanoscale
https://www.readbyqxmd.com/read/29767820/-role-of-visceral-surgery-in-oligometastases-of-non-gastrointestinal-tumors
#14
REVIEW
R Wahba, D Stippel, C Bruns
BACKGROUND: Patients with oligometastatic disease can benefit from local treatment of the metastases. Under these premises the resection of liver metastases and visceral metastases of non-gastrointestinal tumors is performed increasingly more frequently in selected patients. The aim of this study was to evaluate the role of visceral oncological surgery in hepatic oligometastatic disease of non-gastrointestinal tumors according to the currently available literature. MATERIAL AND METHODS: A systematic search of MEDLINE and PubMed was carried out focusing on the topics of oligometastases, liver resection and metastectomy for breast cancer, renal cell carcinoma, malignant melanoma, ovarian cancer and non-small cell lung cancer...
May 16, 2018: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/29767260/rnai%C3%A2-mediated-downregulation-of-asparaginase%C3%A2-like-protein-1-inhibits-growth-and-promotes-apoptosis-of-human-cervical-cancer-line-siha
#15
Xiao-Feng Lv, Han-Qing Hong, Ling Liu, Shi-Hong Cui, Chen-Chen Ren, Hong-Yu Li, Xiao-An Zhang, Lin-Dong Zhang, Tian-Xiang Wei, Jin-Jin Liu, Wen-Ying Xing, Han Fu, Shu-Jun Yan
Asparaginase like 1 (ASRGL1) protein belongs to the N‑terminal nucleophile group, cleaving the isoaspartyl‑dipeptides and L‑asparagine by adding water. It tends to be overexpressed in cancerous tumors including ovarian cancer and breast tumors. The present study assessed the potential ability of ASRGL1 as a molecular target in gene‑based cervical cancer treatment. The protein expression level of ASRGL1 was determined in paraffin‑embedded tumor specimen by immunohistochemistry. Additionally, in order to assess the activity of ASRGL1 during the process of cervical cancer cell multiplication, ASRGL1‑short hairpin (sh) RNA‑expressing lentivirus was established, which was used to infect SiHa cells...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29765553/acquired-resistance-to-everolimus-in-aromatase-inhibitor-resistant-breast-cancer
#16
Mariko Kimura, Toru Hanamura, Kouki Tsuboi, Yosuke Kaneko, Yuri Yamaguchi, Toshifumi Niwa, Kazutaka Narui, Itaru Endo, Shin-Ichi Hayashi
We previously reported the establishment of several types of long-term estrogen-depleted-resistant (EDR) cell lines from MCF-7 breast cancer cells. Type 1 EDR cells exhibited the best-studied mechanism of aromatase inhibitor (AI) resistance, in which estrogen receptor (ER) expression remained positive and PI3K signaling was upregulated. Type 2 EDR cells showed reduced ER activity and upregulated JNK-related signaling. The mTOR inhibitor everolimus reduced growth in cells similar to Type 1 EDR cells. The present study generated everolimus-resistant (EvR) cells from Types 1 and 2 EDR cells following long-term exposure to everolimus in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765247/progression-free-survival-time-to-progression-as-a-potential-surrogate-for-overall-survival-in-hr-her2-metastatic-breast-cancer
#17
Anna Forsythe, David Chandiwana, Janina Barth, Marroon Thabane, Johan Baeck, Gabriel Tremblay
Background: Several recent randomized controlled trials (RCTs) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) have demonstrated significant improvements in progression-free survival (PFS); however, few have reported improvement in overall survival (OS). The surrogacy of PFS or time to progression (TTP) for OS has not been formally investigated in HR+, HER2- MBC. Methods: A systematic literature review of RCTs in HR+, HER2- MBC was conducted to identify studies that reported both median PFS/TTP and OS...
2018: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29764866/lrrc15-is-a-novel-mesenchymal-protein-and-stromal-target-for-antibody-drug-conjugates
#18
James W Purcell, Sonia G Tanlimco, Jonathan A Hickson, Melvin Fox, Mien Sho, Lisa Durkin, Tamar Uziel, Rick Powers, Kelly D Foster-Duke, Thomas McGonigal, Subashri Kumar, Josue Samayoa, Dong Zhang, Joann P Palma, Sasmita Mishra, Diane Hollenbaugh, Kurt Gish, Susan E Morgan-Lappe, Eric D Hsi, Debra T Chao
Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764450/evaluation-of-target-dose-inhomogeneity-in-breast-cancer-treatment-due-to-tissue-elemental-differences
#19
A Fogliata, F De Rose, A Stravato, G Reggiori, S Tomatis, M Scorsetti, L Cozzi
BACKGROUND: Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues. METHODS: CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV_lob and CTV_fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system...
May 15, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29764158/what-is-the-role-of-immunotherapy-in-breast-cancer
#20
Tira J Tan, Jack J Chan, Sulastri Kamis, Rebecca Alexandra Dent
The immune system plays a complex role in the recognition/prevention, early eradication as well as progression of cancer. Recently, we have witnessed great momentum in the field of immuno-oncology. Checkpoint inhibitors and chimeric antigen receptor T cell therapy have now entered the clinic, with impressive and durable clinical responses seen across a broad array of tumor types. There are several lines of evidence supporting the development of an immune targeted approach in breast cancer. Emerging data of early clinical trials evaluating monotherapy checkpoint inhibition have shown modest activity in breast cancer, in particular high grade and aggressive subtypes such as triple negative, human epidermal growth factor receptor 2 (HER2)-positive and luminal B breast cancers...
April 2018: Chinese Clinical Oncology
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