keyword
MENU ▼
Read by QxMD icon Read
search

Lapatinib resistance

keyword
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#1
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#2
Lingxiao Cheng, Yuchen Jin, Min Liu, Maomei Ruan, Libo Chen
Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with radioiodine represents a good choice for radioiodine-refractory differentiated thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance mechanism, and combination with HER inhibitor to prevent MAPK rebound may sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To evaluate if inhibiting both BRAF/MEK and HER can produce stronger redifferetiation effect, we tested the effects of BRAF/MEK inhibitor dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on the expression and function of iodine- and glucose-handling genes in BRAFV600E-positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement as control...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415602/errf-sensitizes-erbb2-positive-breast-cancer-cells-to-lapatinib-treatment-likely-by-attenuating-mcl1-and-erbb2-expression
#3
Leilei Qi, Baotong Zhang, Shiying Zhang, Xinpei Ci, Qiao Wu, Gui Ma, Ang Luo, Liya Fu, Jamie L King, Rita Nahta, Jin-Tang Dong
Previously we found that the estrogen receptor (ER) related factor ERRF regulates cell proliferation and tumor growth, and its expression is positively associated with ER status and better survival but inversely associated with ERBB2 (also named HER2) status in breast cancer. Here we report that ERRF also plays an important role in the response of ERBB2-positive breast cancer cells to lapatinib, a dual tyrosine kinase inhibitor that interrupts the ERBB2 and EGFR pathway. In ERBB2-positive breast cancer cell lines, lower levels of ERRF expression correlated with lapatinib resistance, restoration of ERRF expression in lapatinib-resistant cell lines JIMT-1 and MDA-MB-453 enhanced their lapatinib responses, and knockdown of ERRF in lapatinib sensitive cell lines BT-474 and SK-BR-3 caused lapatinib resistance...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28393315/identification-and-characterization-of-biomarkers-and-their-functions-for-lapatinib-resistant-breast-cancer
#4
Liang Zhang, Yi Huang, Wenlei Zhuo, Yi Zhu, Bo Zhu, Zhengtang Chen
Lapatinib, a novel oral dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways, has presented beneficial effects on breast cancer with positive HER2. However, its efficacy is largely limited by the occurrence of acquired drug resistance. In this study, we aimed to explore the underlying molecular mechanisms of Lapatinib resistance using bioinformatics strategies. The gene expression profile of SKBR3-R (acquired Lapatinib-resistant) and SKBR3 (Lapatinib-sensitive) cell line was downloaded from gene expression omnibus database...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28381415/her2-overexpressing-breast-cancers-amplify-fgfr-signaling-upon-acquisition-of-resistance-to-dual-therapeutic-blockade-of-her2
#5
Ariella B Hanker, Joan G Garrett, Monica Valeria Estrada, Preston D Moore, Paula G Ericsson, James P Koch, Emma Langley, Sharat Singh, Phillip S Kim, Garrett M Frampton, Eric M Sanford, Philip Owns, Jennifer Becker, M Reid Groseclose, Stephen Castellino, Heikki Joensuu, Jens Huober, Jan C Brase, Majjaj Samira, Sylvain Brohée, David Venet, David Brown, José Baselga, Martine Piccart, Christos Sotiriou, Carlos L Arteaga
Dual blockade of HER2 with trastuzumab and lapatinib or pertuzumab has been shown to be superior to single-agent trastuzumab. However, a significant fraction of HER2-overexpressing (HER2+) breast cancers escape from these drug combinations. In this study, we sought to discover the mechanisms of acquired resistance to the combination of lapatinib + trastuzumab.<br /><br />Experimental Design: HER2+ BT474 xenografts were treated with lapatinib + trastuzumab long-term until resistance developed. Potential mechanisms of acquired resistance were evaluated in lapatinib + trastuzumab-resistant (LTR) tumors by targeted capture next-generation sequencing...
April 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28343375/foxo1-suppression-is-a-determinant-of-acquired-lapatinib-resistance-in-her2-positive-gastric-cancer-cells-through-met-upregulation
#6
Jinju Park, Yiseul Choi, Young San Ko, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Min A Kim, Jae-Seon Lee, Mee Soo Chang, Jong-Wan Park, Byung Lan Lee
Purpose: Lapatinib is a candidate drug for treatment of trastuzumab-resistant, HER2-positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box protein O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells. Materials and Methods: Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib...
March 24, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28288164/bayesian-model-of-signal-rewiring-reveals-mechanisms-of-gene-dysregulation-in-acquired-drug-resistance-in-breast-cancer
#7
A K M Azad, Alfons Lawen, Jonathan M Keith
Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks...
2017: PloS One
https://www.readbyqxmd.com/read/28255362/her-family-receptors-are-important-theranostic-biomarkers-for-cervical-cancer-blocking-glucose-metabolism-enhances-the-therapeutic-effect-of-her-inhibitors
#8
Olga Martinho, Renato Silva-Oliveira, Fernanda P Cury, Ana Martins Barbosa, Sara Granja, Adriane Feijó Evangelista, Fábio Marques, Vera Miranda-Gonçalves, Diana Cardoso-Carneiro, Flávia E de Paula, Maicon Zanon, Cristovam Scapulatempo-Neto, Marise A R Moreira, Fátima Baltazar, Adhemar Longatto-Filho, Rui Manuel Reis
Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness...
2017: Theranostics
https://www.readbyqxmd.com/read/28250972/antitumor-effects-of-naturally-occurring-cardiac-glycosides-convallatoxin-and-peruvoside-on-human-er-and-triple-negative-breast-cancers
#9
Vivek Kaushik, Neelam Azad, Juan Sebastian Yakisich, Anand Krishnan V Iyer
Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal growth factor receptor 2 (HER2). Hormone receptor-positive and HER2-enriched cancers can be targeted using hormone and HER2-targeting therapies such as trastuzumab or lapatinib. However, triple-negative breast cancers (TNBCs) do not express any of the receptors and therefore are resistant to most targeted therapies, and cytotoxic chemotherapies are the only viable option available for the treatment of TNBCs...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28229982/circulating-free-dna-mutation-associated-with-response-of-targeted-therapy-in-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer
#10
Qing Ye, Fan Qi, Li Bian, Shao-Hua Zhang, Tao Wang, Ze-Fei Jiang
BACKGROUND: The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA)...
March 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28228709/targeted-therapies-in-her2-overexpressing-metastatic-breast-cancer
#11
REVIEW
Soumaya Labidi, Nesrine Mejri, Aymen Lagha, Nouha Daoud, Houda El Benna, Mehdi Afrit, Hamouda Boussen
Human epidermal growth factor receptor-2 (HER2) is amplified in 25-30% of breast cancers and is associated with aggressive disease and poorer survival. Multiple anti-HER2 targeted therapies have dramatically changed management and outcome of this subgroup, both in adjuvant and metastatic settings. Despite the improvement of survival thanks to trastuzumab, unclear mechanisms of resistance occur, which has led to the development of new anti-HER2 therapies such as lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1)...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28209619/lapatinib-resistance-in-breast-cancer-cells-is-accompanied-by-phosphorylation-mediated-reprogramming-of-glycolysis
#12
Benjamin Ruprecht, Esther A Zaal, Jana Zecha, Wei Wu, Celia R Berkers, Bernhard Kuster, Simone Lemeer
HER2/ERBB2-overexpressing breast cancers targeted effectively by the small-molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In this study, we employed explorative mass spectrometry to profile proteome, kinome, and phosphoproteome changes in an established model of lapatinib resistance to systematically investigate initial inhibitor response and subsequent reprogramming in resistance. The resulting dataset, which collectively contains quantitative data for >7,800 proteins, >300 protein kinases, and >15,000 phosphopeptides, enabled deep insight into signaling recovery and molecular reprogramming upon resistance...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28165387/concurrent-autophagy-inhibition-overcomes-the-resistance-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-human-bladder-cancer-cells
#13
Minyong Kang, Kyoung-Hwa Lee, Hye Sun Lee, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Ja Hyeon Ku
Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28158234/yes1-signaling-mediates-the-resistance-to-trastuzumab-lap-atinib-in-breast-cancer
#14
Tatsuaki Takeda, Hiromasa Yamamoto, Hirotaka Kanzaki, Ken Suzawa, Takahiro Yoshioka, Shuta Tomida, Xiaojiang Cui, Ramachandran Murali, Kei Namba, Hiroki Sato, Hidejiro Torigoe, Mototsugu Watanabe, Kazuhiko Shien, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Yoshihisa Kitamura, Shinichiro Miyoshi, Toshiaki Sendo, Shinichi Toyooka
BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in approximately 15-23% of breast cancers and these cancers are classified as HER2-positive breast cancer. Trastuzumab is the first-line targeted therapeutic drug for HER2-positive breast cancer and has improved patient overall survival. However, acquired resistance to trastuzumab is still a critical issue in breast cancer treatment. We previously established a trastuzumab-resistant breast cancer cell line (named as BT-474-R) from a trastuzumab-sensitive HER2-amplified cell line BT-474...
2017: PloS One
https://www.readbyqxmd.com/read/28152547/neratinib-resistance-and-cross-resistance-to-other-her2-targeted-drugs-due-to-increased-activity-of-metabolism-enzyme-cytochrome-p4503a4
#15
Susan Breslin, Michelle C Lowry, Lorraine O'Driscoll
BACKGROUND: Neratinib is in Phase 3 clinical trials but, unfortunately, the development of resistance is inevitable. Here, we investigated the effects of acquired neratinib resistance on cellular phenotype and the potential mechanism of this resistance. METHODS: Neratinib-resistant variants of HER2-positive breast cancer cells were developed and their cross-resistance investigated using cytotoxicity assays. Similarly, sensitivity of trastuzumab-resistant and lapatinib-resistant cells to neratinib was assessed...
February 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#16
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059154/abcg2-overexpressing-h460-mx20-cell-xenografts-in-athymic-nude-mice-maintained-original-biochemical-and-cytological-characteristics
#17
Wei Zhang, Zhen Chen, Likun Chen, Fang Wang, Furong Li, Xiaokun Wang, Liwu Fu
H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone's induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032592/feedback-activation-of-her3-attenuates-response-to-egfr-inhibitors-in-colon-cancer-cells
#18
Albert Bosch-Vilaró, Bart Jacobs, Valentina Pomella, Layka Abbasi Asbagh, Richard Kirkland, Joe Michel, Sharat Singh, Xinjun Liu, Phillip Kim, Gregory Weitsman, Paul R Barber, Borivoj Vojnovic, Tony Ng, Sabine Tejpar
The EGFR inhibitor cetuximab is approved for the treatment of colorectal cancer. However, both innate and acquired resistance mechanisms, including compensatory feedback loops, limit its efficacy. Nevertheless, the emergence of these feedback loops has remained largely unexplored to date. Here, we showed feedback upregulation of HER3 and induction of HER3 phosphorylation after cetuximab treatment in colon cancer cells. We also showed that this upregulation occurs, at least partly, through AKT inhibition. Together with this, we observed increased HER2:HER3 dimerization upon cetuximab treatment...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27942916/synergistic-disruption-of-er%C3%AE-her2-crosstalk-by-endoxifen-and-lapatinib-in-breast-cancer-cells
#19
James Chun Yip Chan, Pei Shi Ong, Peirong Lim, Preben Xiang Long Teng, Eric Chun Yong Chan
BACKGROUND: Despite decades of clinical success, tamoxifen therapy is complicated by inter-individual variability due to CYP450 polymorphism and resistance attributed to ERα/HER2 crosstalk. Direct administration of endoxifen shows promise in circumventing obligatory CYP450 bioactivation while maintaining efficacy. Separately, disruption of the crosstalk using probe antagonists against ERα (tamoxifen) and HER2 (e.g., lapatinib) has been explored clinically. However, the efficacy of this combination may be confounded by lapatinib, a potent inactivator of CYP3A4/5 which could negate the bioactivation of tamoxifen to the active metabolite endoxifen...
January 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27903634/distinct-receptor-tyrosine-kinase-subsets-mediate-anti-her2-drug-resistance-in-breast-cancer
#20
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...
January 13, 2017: Journal of Biological Chemistry
keyword
keyword
5320
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"