keyword
MENU ▼
Read by QxMD icon Read
search

Lapatinib resistance

keyword
https://www.readbyqxmd.com/read/29333945/remarkable-response-with-pembrolizumab-plus-albumin-bound-paclitaxel-in-2-cases-of-her2-positive-metastatic-breast-cancer-who-have-failed-to-multi-anti-her2-targeted-therapy
#1
Bian Li, Wang Tao, Zhang Shao-Hua, Q U Ze-Rui, Jin Fu-Quan, L I Fan, Jiang Ze-Fei
In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab,lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients.Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab(2mg/Kg, day1) plus albumin-bound paclitaxel(125mg/m2, day1,8) every 3 weeks.CT evaluation and HER2 ECD test were performed every 2 cycles...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29330210/trastuzumab-plus-pertuzumab-resistance-does-not-preclude-response-to-lapatinib-plus-trastuzumab-in-her2-amplified-colorectal-cancer
#2
Marwan G Fakih
Human epidermal growth factor 2 (HER2) amplification represents a distinct molecular subgroup of colorectal cancers that is associated with anti-epidermal growth factor receptor resistance and sensitivity to dual HER2 targeting. Although clinical trials have reported activity for trastuzumab/pertuzumab and trastuzumab/lapatinib combinations, there are no reports on lapatinib plus trastuzumab activity after resistance to trastuzumab plus pertuzumab. Presented are three cases of HER2 amplified colorectal cancer that developed acquired refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance...
January 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29326440/braf-inhibition-upregulates-a-variety-of-receptor-tyrosine-kinases-and-their-downstream-effector-gab2-in-colorectal-cancer-cell-lines
#3
Ricarda Herr, Sebastian Halbach, Miriam Heizmann, Hauke Busch, Melanie Boerries, Tilman Brummer
BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with poor prognosis. Inhibitors selective for the BRAFV600E oncoprotein, the most common BRAF mutant, elicit only poor response rates in BRAF-mutant CRC as single agents. This unresponsiveness was mechanistically attributed to the loss of negative feedbacks on the epidermal growth factor receptor (EGFR) and initiated clinical trials that combine BRAF (and MEK) inhibitors, either singly or in combination, with the anti-EGFR antibodies cetuximab or panitumumab...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#4
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29285221/a-c-jun-n-terminal-kinase-inhibitor-jnk-in-8-sensitizes-triple-negative-breast-cancer-cells-to-lapatinib
#5
Nancy D Ebelt, Tamer S Kaoud, Ramakrishna Edupuganti, Sabrina Van Ravenstein, Kevin N Dalby, Carla L Van Den Berg
Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor, inhibitors such as lapatinib have not shown therapeutic efficacy in TNBC patients. Herein, we report that treatment with the covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death, while these compounds as single agents have little effect...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274446/a-progressively-enlarging-cerebellar-hematoma-concurrent-with-t-dm1-treatment-case-report
#6
Marcelo D Vilela, William T Longstreth, Hugo As Pedrosa, Gabriel Ob Gil, Juliano M Duarte, Marco Antonio D Filho
BACKGROUND: Trastuzumab emtansine, an antibody-drug conjugate commonly abbreviated as T-DM1, is accepted as an effective therapy for trastuzumab-resistant metastatic HER2-positive breast cancer. T-DM1 significantly increases progression-free and overall survival when compared to lapatinib plus capecitabine in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane. Among the common side effects related to T-DM1, thrombocytopenia and mucosal hemorrhage are seen, although they are infrequently judged to be clinically significant...
December 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29231164/lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-a%C3%A2-systematic-review%C3%A2
#7
Rebecca Madden, Sam Kosari, Gregory M Peterson, Nasser Bagheri, Jackson Thomas
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine...
December 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29223420/her2-confers-resistance-to-foretinib-inhibition-of-met-amplified-esophageal-adenocarcinoma-cells
#8
Alexei A Goltsov, Bingliang Fang, Tej K Pandita, Dipen M Maru, Stephen G Swisher, Wayne L Hofstetter
BACKGROUND: Recent genomic studies indicated that esophageal adenocarcinoma (EAC) is driven by amplification of c-MET or HER2 or both in a subset of patients. We studied the effect of MET targeting by the small molecule inhibitor foretinib in EAC cells and the interplay between MET and HER2 signaling. METHODS: We measured the expression levels and phosphorylation status of MET and HER2 proteins in EAC cell lines using Western blot analysis. The expression levels of MET and HER2 were manipulated by transfecting cells with specific siRNA or a plasmid expressing HER2...
December 6, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#9
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162825/outcomes-of-patients-with-sarcoma-enrolled-in-clinical-trials-of-pazopanib-combined-with-histone-deacetylase-mtor-her2-or-mek-inhibitors
#10
Vikas Dembla, Roman Groisberg, Ken Hess, Siqing Fu, Jennifer Wheler, David S Hong, Filip Janku, Ralph Zinner, Sarina Anne Piha-Paul, Vinod Ravi, Robert S Benjamin, Shreyaskumar Patel, Neeta Somaiah, Cynthia E Herzog, Daniel D Karp, Jason Roszik, Funda Meric-Bernstam, Vivek Subbiah
Pazopanib is US FDA approved for the treatment of advanced soft tissue sarcomas. All patients with this disease ultimately develop resistance to therapy. Mechanisms of resistance include activation of the mTOR, histone deacetylase (HDAC), MAPK, and ERBB4 pathways. We hypothesized that combining pazopanib with other targeted agents inhibiting these pathways would increase response rates. We retrospectively evaluated the safety and efficacy of pazopanib plus vorinostat, everolimus, lapatinib or trastuzumab, and MEK inhibitor in patients with advanced sarcoma...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29159332/a-biomaterial-screening-approach-reveals-microenvironmental-mechanisms-of-drug-resistance
#11
Alyssa D Schwartz, Lauren E Barney, Lauren E Jansen, Thuy V Nguyen, Christopher L Hall, Aaron S Meyer, Shelly R Peyton
Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment...
November 21, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29156708/a-preclinical-evaluation-of-the-mek-inhibitor-refametinib-in-her2-positive-breast-cancer-cell-lines-including-those-with-acquired-resistance-to-trastuzumab-or-lapatinib
#12
John O'Shea, Mattia Cremona, Clare Morgan, Malgorzata Milewska, Frankie Holmes, Virginia Espina, Lance Liotta, Joyce O'Shaughnessy, Sinead Toomey, Stephen F Madden, Aoife Carr, Naomi Elster, Bryan T Hennessy, Alex J Eustace
Purpose: The MEK/MAPK pathway is commonly activated in HER2-positive breast cancer, but little investigation of targeting this pathway has been undertaken. Here we present the results of an in vitro preclinical evaluation of refametinib, an allosteric MEK1/2 inhibitor, in HER2-positive breast cancer cell lines including models of acquired resistance to trastuzumab or lapatinib. Methods: A panel of HER2-positive breast cancer cells were profiled for mutational status and also for anti-proliferative response to refametinib alone and in combination with the PI3K inhibitor (PI3Ki) copanlisib and the HER2-targeted therapies trastuzumab and lapatinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154981/egfr-family-inhibition-identifies-p38-mapk-as-a-potential-therapeutic-target-in-bladder-cancer
#13
Regina Mora Vidal, Sergio Regufe da Mota, Annette Hayden, Hannah Markham, James Douglas, Graham Packham, Simon J Crabb
Objective To investigate perturbations in downstream signalling pathway activation and potential resistance mechanisms to EGFR and/or HER2 inhibition in cell line models of bladder cancer. Methods We undertook a structured screening approach by phosphokinase array, followed by validation steps, to detect activated downstream signalling pathway nodes after therapeutic inhibition of EGFR and/or HER2 in bladder cancer cell lines. Results Erlotinib treatment of RT112 cells induced phosphorylation of 9 activated phospho-protein targets (p38 MAPK (Thr180/Tyr182), GSK-3α/β (Ser21/9), MEK1/2 (Ser218/222, Ser222/226), Akt (Ser473), TOR (Ser2448), Src (Tyr419), p27 (Thr198), p27 (Thr157) and PLCγ-1 (Tyr783)) whereas STAT4 (Tyr693) phosphorylation was reduced...
November 15, 2017: Urology
https://www.readbyqxmd.com/read/29110152/low-pten-levels-and-pik3ca-mutations-predict-resistance-to-neoadjuvant-lapatinib-and-trastuzumab-without-chemotherapy-in-patients-with-her2-over-expressing-breast-cancer
#14
Mothaffar F Rimawi, Carmine De Angelis, Alejandro Contreras, Fresia Pareja, Felipe C Geyer, Kathleen A Burke, Sabrina Herrera, Tao Wang, Ingrid A Mayer, Andres Forero, Rita Nanda, Matthew P Goetz, Jenny C Chang, Ian E Krop, Antonio C Wolff, Anne C Pavlick, Suzanne A W Fuqua, Carolina Gutierrez, Susan G Hilsenbeck, Marilyn M Li, Britta Weigelt, Jorge S Reis-Filho, C Kent Osborne, Rachel Schiff
PURPOSE: Aberrant activation of the PI3K pathway has been implicated in resistance to HER2-targeted therapy, but results of clinical trials are confounded by the co-administration of chemotherapy. We investigated the effect of perturbations of this pathway in breast cancers from patients treated with neoadjuvant anti-HER2-targeted therapy without chemotherapy. PATIENTS AND METHODS: Baseline tumor samples from patients with HER2-positive breast cancer enrolled in TBCRC006 (NCT00548184), a 12-week neoadjuvant clinical trial with lapatinib plus trastuzumab [plus endocrine therapy for estrogen receptor (ER)-positive tumors], were assessed for PTEN status by immunohistochemistry and PIK3CA mutations by sequencing...
November 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29100507/inhibition-of-pi3k-akt-mtor-overcomes-cisplatin-resistance-in-the-triple-negative-breast-cancer-cell-line-hcc38
#15
Katharina Gohr, Alexandra Hamacher, Laura H Engelke, Matthias U Kassack
BACKGROUND: Widely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings. METHODS: The TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3...
November 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29100278/somatic-mutations-in-salivary-duct-carcinoma-and-potential-therapeutic-targets
#16
Timothy K Khoo, Bing Yu, Joel A Smith, Angus J Clarke, Peter P Luk, Christina I Selinger, Kate L Mahon, Spiridoula Kraitsek, Carsten Palme, Michael J Boyer, Marcel E Dinger, Mark J Cowley, Sandra A O'Toole, Jonathan R Clark, Ruta Gupta
Background: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29078212/-current-status-of-targeted-treatment-in-breast-cancer
#17
Katharina Seiffert, Barbara Schmalfeldt, Volkmar Müller
Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival...
November 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29069787/proteasome-inhibitors-prevent-bi-directional-her2-estrogen-receptor-cross-talk-leading-to-cell-death-in-endocrine-and-lapatinib-resistant-her2-er-breast-cancer-cells
#18
Sonja Thaler, Marcus Schmidt, Sven Roβwag, Gitta Thiede, Arno Schad, Jonathan P Sleeman
Amplification and/or overexpression of the human epidermal growth factor 2 (HER2) oncogene occurs in about 13-15% of invasive breast cancer and triggers breast cancer cell proliferation, survival and metastatic progression. Around half of all breast cancers with HER2 overexpression co-express hormone receptors (HR) such as those for estrogen and progesterone. Aberrant signaling through HER2 and other members of the HER-family mediates endocrine-resistance in estrogen receptor alpha (ERα) positive breast cancer...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29059433/an-erbb1-3-neutralizing-antibody-mixture-with-high-activity-against-drug-resistant-her2-breast-cancers-with-erbb-ligand-overexpression
#19
Luis J Schwarz, Katherine E Hutchinson, Brent N Rexer, Mónica Valeria Estrada, Paula I Gonzalez Ericsson, Melinda E Sanders, Teresa C Dugger, Luigi Formisano, Angel Guerrero-Zotano, Monica Red-Brewer, Christian D Young, Johan Lantto, Mikkel W Pedersen, Michael Kragh, Ivan D Horak, Carlos L Arteaga
Background: Plasticity of the ERBB receptor network has been suggested to cause acquired resistance to anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we studied whether a novel approach using an ERBB1-3-neutralizing antibody mixture can block these compensatory mechanisms of resistance. Methods: HER2+ cell lines and xenografts (n ≥ 6 mice per group) were treated with the ERBB1-3 antibody mixture Pan-HER, trastuzumab/lapatinib (TL), trastuzumab/pertuzumab (TP), or T-DM1...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29020637/combinatorial-microenvironments-impose-a-continuum-of-cellular-responses-to-a-single-pathway-targeted-anti-cancer-compound
#20
Chun-Han Lin, Tiina Jokela, Joe Gray, Mark A LaBarge
Tumor microenvironments are a driver of resistance to anti-cancer drugs. Dissecting cell-microenvironment interactions into tractable units of study presents a challenge. Here, we assess the impact of hundreds of tumor-inspired microenvironments, in parallel, on lapatinib responses in four cancer cell lines. Combinations of ECM and soluble factors were printed on stiffness-tunable substrata to generate a collection of controlled microenvironments in which to explore cell-based functional responses. Proliferation, HER2 protein expression and phosphorylation, and morphology were measured in single cells...
October 10, 2017: Cell Reports
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"