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https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#1
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29684854/the-role-of-her2-nrf2-axis-in-induction-of-oxaliplatin-resistance-in-colon-cancer-cells
#2
Abbas Pirpour Tazehkand, Maryam Akbarzadeh, Kobra Velaie, Mohammad Reza Sadeghi, Nasser Samadi
Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in promoting chemoresistance by regulation of antioxidants and detoxification enzymes. Her2 is a member of tyrosine kinase receptor family with a key function in resistance of cancer cells to chemotherapeutics. The aim of this study was to investigate the possible cross talk between Nrf2 and Her2 mediated signaling pathways in development of oxaliplatin resistance in colon cancer cells. We first generated oxaliplatin-resistant LS174T and SW480 colon cancer cells with different Her2 expression levels by employing IC50 concentrations followed by a resting period...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29496094/clinical-trials-and-progress-in-metastatic-colon-cancer
#3
REVIEW
Kabir Mody, Tanios Bekaii-Saab
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide but associated mortality has declined in recent decades. Genomic profiling of the disease has resulted in the definition of subsets of patients-for example, KRAS, NRAS, or BRAF mutated; Her2 amplified; and mismatch repair deficient-which has enabled personalization of therapeutic decision making. These subsets are guiding drug development and combination therapy approaches using both targeted therapies and immunotherapies. Further refinement based on molecular discoveries and the emergence of newer technologies to enable new discoveries allow for great optimism for the future on behalf of patients with colon cancer...
April 2018: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/29492918/-surgical-treatment-and-prognosis-of-borrmann-type-iiii-gastric-cancer-involving-the-whole-stomach
#4
Ruizeng Dong, Zewei Zhang, Yiming Zhou, Yonghong Hua, Jianmin Guo
OBJECTIVE: To explore the surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach. METHODS: Clinicopathological characteristics and survival data of 223 patients with Borrmann type IIII( gastric cancer involving the whole stomach (defined as the tumor infiltrating 3 regions of the stomach) receiving surgical treatment at the Department of Abdominal Surgery of Zhejiang Cancer Hospital between January 2002 and December 2015 were analyzed retrospectively...
February 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/29477636/preclinical-analysis-of-jaa-f11-a-specific-anti-thomsen-friedenreich-antibody-via-immunohistochemistry-and-in-vivo-imaging
#5
Loukia G Karacosta, John C Fisk, Joseph Jessee, Swetha Tati, Bradley Turner, Diala Ghazal, Rachel Ludwig, Holly Johnson, Julia Adams, Munawwar Sajjad, Steven Koury, Rene Roy, James R Olson, Kate Rittenhouse-Olson
The tumor specificity of JAA-F11, a novel monoclonal antibody specific for the Thomsen-Friedenreich cancer antigen (TF-Ag-alpha linked), has been comprehensively studied by in vitro immunohistochemical (IHC) staining of human tumor and normal tissue microarrays and in vivo biodistribution and imaging by micro-positron emission tomography imaging in breast and lung tumor models in mice. The IHC analysis detailed herein is the comprehensive biological analysis of the tumor specificity of JAA-F11 antibody performed as JAA-F11 is progressing towards preclinical safety testing and clinical trials...
April 2018: Translational Oncology
https://www.readbyqxmd.com/read/29394723/-a-case-report-of-gastric-cancer-with-positive-peritoneal-lavage-cytology-and-metachronous-schnitzler-s-metastasis-treated-with-multimodality-therapy
#6
Masaru Udagawa, Yuuki Mizuno, Iichirou Ohnishi, Tetsuo Sugishita, Satoru Kakuta, Yoshiki Murase, Yuuichirou Watanabe, Rama Adikrisna
A69 -year-old male patient with type 3 gastric cancer in pyloric antrum underwent distal gastrectomy with regional lymphadenectomy. Serosal infiltration of cancer tissue was found in the anterior wall of antrum, and the evaluation of peritoneal lavage cytology were positive. Pathological analysis showed the tumor was mainly consist of moderately tubular adenocarcinoma and strongly positive for HER2 stain. Postoperatively, combined therapy of capecitabine and trastuzumab was carried out, but cisplatin was excluded because of the patient's rejection...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29387480/sequential-her2-blockade-as-effective-therapy-in-chemorefractory-her2-gene-amplified-ras-wild-type-metastatic-colorectal-cancer-learning-from-a-clinical-case
#7
Erika Martinelli, Teresa Troiani, Vincenzo Sforza, Giulia Martini, Claudia Cardone, Pietro Paolo Vitiello, Davide Ciardiello, Anna Maria Rachiglio, Nicola Normanno, Andrea Sartore-Bianchi, Silvia Marsoni, Alberto Bardelli, Salvatore Siena, Fortunato Ciardiello
Background: Constitutive activation of HER2-dependent intracellular signalling by HER2 gene amplification or by HER2 mutations has been demonstrated as a mechanism of primary and secondary cancer resistance to cetuximab or panitumumab in preclinical and clinical models of metastatic colorectal cancer (mCRC). Both HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) cohort A and My Pathway clinical trials provided clinical evidence that anti-HER2 therapies could be active in these patients...
2018: ESMO Open
https://www.readbyqxmd.com/read/29367538/breast-cancer-clinical-trial-of-chemotherapy-and-trastuzumab-potential-tool-to-identify-cardiac-modifying-variants-of-dilated-cardiomyopathy
#8
Daniel J Serie, Julia E Crook, Brian M Necela, Bianca C Axenfeld, Travis J Dockter, Gerardo Colon-Otero, Edith A Perez, E Aubrey Thompson, Nadine Norton
Doxorubicin and the ERBB2 targeted therapy, trastuzumab, are routinely used in the treatment of HER2+ breast cancer. In mouse models, doxorubicin is known to cause cardiomyopathy and conditional cardiac knock out of Erbb2 results in dilated cardiomyopathy and increased sensitivity to doxorubicin-induced cell death. In humans, these drugs also result in cardiac phenotypes, but severity and reversibility is highly variable. We examined the association of decline in left ventricular ejection fraction (LVEF) at 15,204 single nucleotide polymorphisms (SNPs) spanning 72 cardiomyopathy genes, in 800 breast cancer patients who received doxorubicin and trastuzumab...
May 4, 2017: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29338072/targeting-her2-in-colorectal-cancer-the-landscape-of-amplification-and-short-variant-mutations-in-erbb2-and-erbb3
#9
Jeffrey S Ross, Marwan Fakih, Siraj M Ali, Julia A Elvin, Alexa B Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, James Sun, Vincent A Miller, Philip J Stephens, Laurie M Gay
BACKGROUND: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability...
April 1, 2018: Cancer
https://www.readbyqxmd.com/read/29315012/development-of-an-anti-her2-monoclonal-antibody-h2mab-139-against-colon-cancer
#10
Mika K Kaneko, Shinji Yamada, Shunsuke Itai, Yukinari Kato
Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H2 Mab-139 (IgG1 , kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses...
February 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29312543/dual-targeting-of-her3-and-mek-may-overcome-her3-dependent-drug-resistance-of-colon-cancers
#11
Giulia Bon, Rossella Loria, Carla Azzurra Amoreo, Alessandra Verdina, Isabella Sperduti, Arianna Mastrofrancesco, Silvia Soddu, Maria Grazia Diodoro, Marcella Mottolese, Matilde Todaro, Giorgio Stassi, Michele Milella, Ruggero De Maria, Rita Falcioni
Although the medical treatment of colorectal cancer has evolved greatly in the last years, a significant portion of early-stage patients develops recurrence after therapies. The current clinical trials are directed to evaluate new drug combinations and treatment schedules. By the use of patient-derived or established colon cancer cell lines, we found that the tyrosine kinase receptor HER3 is involved in the mechanisms of resistance to therapies. In agreement, the immunohistochemical analysis of total and phospho-HER3 expression in 185 colorectal cancer specimens revealed a significant correlation with lower disease-free survival...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29172998/establishment-of-h-2-mab-119-an-anti-human-epidermal-growth-factor-receptor-2-monoclonal-antibody-against-pancreatic-cancer
#12
Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Yao-Wen Chang, Hiroyuki Harada, Hiroyoshi Suzuki, Mika K Kaneko, Yukinari Kato
Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H2 Mab-119 (IgG1 , kappa), and characterized its efficacy against pancreatic cancers using flow cytometry, Western blot, and immunohistochemical analyses...
December 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29164052/development-of-novel-patient-derived-xenografts-from-breast-cancer-brain-metastases
#13
María J Contreras-Zárate, D Ryan Ormond, Austin E Gillen, Colton Hanna, Nicole L Day, Natalie J Serkova, Britta M Jacobsen, Susan M Edgerton, Ann D Thor, Virginia F Borges, Kevin O Lillehei, Michael W Graner, Peter Kabos, Diana M Cittelly
Brain metastases are an increasing burden among breast cancer patients, particularly for those with HER2+ and triple negative (TN) subtypes. Mechanistic insight into the pathophysiology of brain metastases and preclinical validation of therapies has relied almost exclusively on intracardiac injection of brain-homing cells derived from highly aggressive TN MDA-MB-231 and HER2+ BT474 breast cancer cell lines. Yet, these well characterized models are far from representing the tumor heterogeneity observed clinically and, due to their fast progression in vivo , their suitability to validate therapies for established brain metastasis remains limited...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29156800/comparative-molecular-analyses-of-left-sided-colon-right-sided-colon-and-rectal-cancers
#14
Mohamed E Salem, Benjamin A Weinberg, Joanne Xiu, Wafik S El-Deiry, Jimmy J Hwang, Zoran Gatalica, Philip A Philip, Anthony F Shields, Heinz-Josef Lenz, John L Marshall
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138581/puma-mediates-the-anti-cancer-effect-of-osimertinib-in-colon-cancer-cells
#15
Lingchuan Guo, Shan Huang, Xinwei Wang
Osimertinib, an irreversible EGFR/HER2 inhibitor, has been found to be effective in the cancer cell with EGFR gene mutations in preclinical lung cancer models. However, the effect of osimertinib in colorectal cancer (CRC) cells is unclear. In the present study, we investigated how osimertinib suppresses CRC cells growth and potentiates effects of other chemotherapeutic drugs. We found that p73-mediated osimertinib-induced p53 upregulated modulator of apoptosis (PUMA) expression irrespective of p53 status following PI3K/AKT pathway inhibition in CRC cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28904862/t-darpp-is-an-elongated-monomer-that-binds-calcium-and-is-phosphorylated-by-cyclin-dependent-kinases-1-and-5
#16
Jamil Momand, Patrycja Magdziarz, You Feng, Dianlu Jiang, Elizabeth Parga, Arianna Celis, Erin Denny, Xiaoying Wang, Martin L Phillips, Estuardo Monterroso, Susan E Kane, Feimeng Zhou
t-Darpp (truncated isoform of dopamine- and cAMP-regulated phosphoprotein) is a protein encoded by the PPP1R1B gene and is expressed in breast, colon, esophageal, gastric, and prostate cancers, as well as in normal adult brain striatal cells. Overexpression of t-Darpp in cultured cells leads to increased protein kinase A activity and increased phosphorylation of AKT (protein kinase B). In HER2+ breast cancer cells, t-Darpp confers resistance to the chemotherapeutic agent trastuzumab. To shed light on t-Darpp function, we studied its secondary structure, oligomerization status, metal-binding properties, and phosphorylation by cyclin-dependent kinases 1 and 5...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28763429/genome-wide-association-study-of-cardiotoxicity-in-the-ncctg-n9831-alliance-adjuvant-trastuzumab-trial
#17
Daniel J Serie, Julia E Crook, Brian M Necela, Travis J Dockter, Xue Wang, Yan W Asmann, DeLisa Fairweather, Katelyn A Bruno, Gerardo Colon-Otero, Edith A Perez, E Aubrey Thompson, Nadine Norton
OBJECTIVES: The major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity. METHODS: The NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer...
October 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28754471/how-to-train-your-inhibitor-design-strategies-to-overcome-resistance-to-epidermal-growth-factor-receptor-inhibitors
#18
REVIEW
Sandra N Milik, Deena S Lasheen, Rabah A T Serya, Khaled A M Abouzid
Epidermal Growth Factor Receptor (EGFR) stands out as a key player in the development of many cancers. Its dysregulation is associated with a vast number of tumors such as non-small-cell lung cancer, colon cancer, head-and-neck cancer, breast and ovarian cancer. Being implicated in the development of a number of the most lethal cancers worldwide, EGFR has long been considered as a focal target for cancer therapies, ever since the FDA approval of "Gefitinib" in 2003 and up to the last FDA approved small molecule EGFR kinase inhibitor "Osimertinib" in 2015...
December 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28736637/primary-and-acquired-resistance-to-biologic-therapies-in-gastrointestinal-cancers
#19
REVIEW
Sam J Lubner, Nataliya V Uboha, Dustin A Deming
Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28662703/the-diagnosis-of-a-metastatic-breast-tumor-from-ovarian-cancer-by-the-succession-of-a-p53-mutation-a-case-report
#20
Ryutaro Mori, Manabu Futamura, Kasumi Morimitsu, Chiemi Saigo, Tatsuhiko Miyazaki, Kazuhiro Yoshida
BACKGROUND: Metastatic breast tumors from other organs are very rare. We herein describe the case of a patient with a metastatic breast tumor due to ovarian cancer who was diagnosed by the succession of a p53 mutation. CASE PRESENTATION: The patient was a 59-year-old woman with sigmoid colon stenosis. Diagnostic imaging revealed a pelvic mass, multiple liver tumors, ascites, and multiple swollen para-aortic lymph nodes, suggesting an advanced ovarian tumor. Transverse loop colostomy and partial resection of the greater omentum was performed followed by six cycles of paclitaxel with carboplatin chemotherapy (TC therapy)...
June 29, 2017: World Journal of Surgical Oncology
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