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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/29672836/pathogenic-and-targetable-genetic-alterations-in-70-urachal-adenocarcinomas
#2
Henning Reis, Kristan E van der Vos, Christian Niedworok, Thomas Herold, Orsolya Módos, Attila Szendrői, Thomas Hager, Marc Ingenwerth, Daniël J Vis, Mark A Behrendt, Jeroen de Jong, Michiel S van der Heijden, Benoit Peyronnet, Romain Mathieu, Marcel Wiesweg, Jason Ablat, Krzysztof Okon, Yuri Tolkach, David Keresztes, Nikolett Nagy, Felix Bremmer, Nadine T Gaisa, Piotr Chlosta, Joerg Kriegsmann, Ilona Kovalszky, József Timar, Glen Kristiansen, Heinz-Joachim Radzun, Ruth Knüchel, Martin Schuler, Peter Black, Herbert Rübben, Boris Hadaschik, Kurt Werner Schmid, Bas W G van Rhijn, Péter Nyirády, Tibor Szarvas
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins (MMR)) and evaluated the microsatellite instability (MSI) status...
April 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29659677/targeting-the-human-epidermal-growth-factor-receptor-2-her2-oncogene-in-colorectal-cancer
#3
S Siena, A Sartore-Bianchi, S Marsoni, H I Hurwitz, S J McCall, F Penault-Llorca, S Srock, A Bardelli, L Trusolino
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. Using functional and genomic analyses of patient-derived xenografts, we previously showed that a subset (approximately 5%) of metastatic colorectal cancer (CRC) tumors are driven by amplification or mutation of HER2. MATERIALS AND METHODS: This paper reviews the role of HER2 as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target in CRC, considering the specifics of HER2 testing in this tumor type...
April 6, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29589315/molecular-testing-for-the-treatment-of-advanced-colorectal-cancer-an-overview
#4
Patrick S Lin, Thomas J Semrad
Concurrent with an expansion in the number of agents available for the treatment of advanced CRC, there has been an increase in our understanding of selection biomarkers to optimize the management of patients with this disease. For CRC patients being considered for anti-EGFR therapy, expanded RAS testing is the standard of care to determine the subset of patients who can benefit from cetuximab or panitumumab in conjunction with chemotherapy. A small fraction of patients have HER2 amplification where emerging data suggest treatment with drugs targeting this alteration...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29541416/targeting-scfv-fc-sctrail-fusion-proteins-to-tumor-cells
#5
Meike Hutt, Sina Fellermeier-Kopf, Oliver Seifert, Lisa C Schmitt, Klaus Pfizenmaier, Roland E Kontermann
Fusion proteins combining hexavalent TRAIL with antibody fragments allow for a targeted delivery and efficient apoptosis induction in tumor cells. Here, we analyzed scFv-Fc-scTRAIL molecules directed against EGFR, HER2, HER3, and EpCAM as well as an untargeted Fc-scTRAIL fusion protein for their potentials to induce cell death both in vitro and in a xenograft tumor model in vivo . The scFv-Fc-scTRAIL fusion protein directed against EGFR as well as the fusion protein directed against EpCAM showed targeting effects on the two tested colorectal carcinoma cell lines Colo205 and HCT116, while a fusion protein targeting HER3 was more effective than untargeted Fc-scTRAIL only on Colo205 cells...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29504811/membranous-or-cytoplasmic-her2-expression-in-colorectal-carcinoma-evaluation-of-prognostic-value-using-both-ihc-bdish
#6
Abdelbaset Buhmeida, Mourad Assidi, Jaudah Al-Maghrabi, Ashraf Dallol, Abdulrahman Sibiany, Mahmoud Al-Ahwal, Adeel Chaudhary, Adel Abuzenadah, Mohammed Al-Qahtani
BACKGROUND: Human epidermal growth factor recptor-2 (HER2) was identified as a driver gene in several types of cancers with both prognostic and predictive value. However, the molecular association of HER2 gene mutation with HER2 gene amplification and/or protein expression in cancer tissues has not been clearly defined. Moreover, there is little information available on HER2 status role in tumor progression and metastasis in colorectal carcinoma (CRC) compared to other solid tumors. The aim of this study was to evaluate both HER2 amplification and protein expression profiles using immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) techniques, respectively...
February 7, 2018: Cancer Investigation
https://www.readbyqxmd.com/read/29496094/clinical-trials-and-progress-in-metastatic-colon-cancer
#7
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/29470838/first-line-cetuximab-monotherapy-in-kras-nras-braf-mutation-negative-colorectal-cancer-patients
#8
Vladimir M Moiseyenko, Fedor V Moiseyenko, Grigoriy A Yanus, Ekatherina Sh Kuligina, Anna P Sokolenko, Ilya V Bizin, Alexey A Kudriavtsev, Svetlana N Aleksakhina, Nikita M Volkov, Vyacheslav A Chubenko, Kseniya S Kozyreva, Mikhail M Kramchaninov, Alexandr S Zhuravlev, Kseniya V Shelekhova, Denis V Pashkov, Alexandr O Ivantsov, Aigul R Venina, Tatyana N Sokolova, Elena V Preobrazhenskaya, Natalia V Mitiushkina, Alexandr V Togo, Aglaya G Iyevleva, Evgeny N Imyanitov
BACKGROUND: Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests...
February 22, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29409930/the-importance-of-egfr-as-a-biomarker-in-molecular-apocrine-breast-cancer
#9
Xiaozhen Liu, Changyun Feng, Junjun Liu, Jian Liu, Congying Li, Cong Xu, Yun Niu
Molecular apocrine breast cancer (MABC) is a molecular subtype with a poor prognosis, and there is urgent need to find new therapeutic targets. Epidermal growth factor receptor (EGFR) plays an important part in regulating the biological behavior of tumor cells, and EGFR-targeted drugs have already been used in therapy for lung and colorectal cancers. The purpose of this study was to analyze the significance of EGFR expression in MABC. A total of 400 patients with invasive breast cancer were analyzed, including 200 MABC and 200 nonMABC cases...
January 30, 2018: Human Pathology
https://www.readbyqxmd.com/read/29394804/-a-case-of-synchronous-quadruple-cancers-treated-with-neoadjuvant-chemotherapy-followed-by-surgery
#10
Keiji Muramoto, Toru Miyake, Tomoharu Shimizu, Hiromichi Sonoda, Tomoyuki Ueki, Yoshitaka Terada, Haruki Mori, Hiromitsu Maehira, Katsushi Takebayashi, Sachiko Kaida, Hiroya Iida, Tsuyoshi Yamaguchi, Masaji Tani
The patient is male in his 60's. He underwent endoscopic examination for anemia, which was found during screening of high PSA value. Endoscopic examination revealed a gastric cancer and 3 colorectal cancers. Histological results from biopsy was HER2 positive poorly differentiated adenocarcinoma in gastric tumor and moderately differentiated adenocarcinoma in colorectal tumor. Chest CT showed a pulmonary nodule in the middle right lung. Histological diagnosis was TTF-1 positive adenocarcinoma, meaning primary lung cancer...
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
#11
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/29361822/ligand-independent-epidermal-growth-factor-receptor-overexpression-correlates-with-poor-prognosis-in-colorectal-cancer
#12
Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Purpose: Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients' survival with CRC. Materials and Methods: The expression of EGFR ligands, including heparin binding epidermal growth factor like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH)...
January 17, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29344282/clinical-significance-of-glycoprotein-non-metastatic-b-and-its-association-with-egfr-her2-in-gastrointestinal-cancer
#13
Jesse Yu Tajima, Manabu Futamura, Siqin Gaowa, Ryutaro Mori, Toshiyuki Tanahashi, Yoshihiro Tanaka, Nobuhisa Matsuhashi, Takao Takahashi, Kazuya Yamaguchi, Tatsuhiko Miyazaki, Kazuhiro Yoshida
Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and motility. We previously reported cross-talk between GPNMB and human epidermal growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might play an important role in resistance to anti-HER2 therapy in breast cancer. Here, we clarified the association between GPNMB and HER-family proteins in gastrointestinal cancer by examining their relationships using gastric and colorectal cancer cell lines...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29338072/targeting-her2-in-colorectal-cancer-the-landscape-of-amplification-and-short-variant-mutations-in-erbb2-and-erbb3
#14
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/29330210/trastuzumab-plus-pertuzumab-resistance-does-not-preclude-response-to-lapatinib-plus-trastuzumab-in-her2-amplified-colorectal-cancer
#15
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...
April 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
#16
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...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29315012/development-of-an-anti-her2-monoclonal-antibody-h2mab-139-against-colon-cancer
#17
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
#18
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/29285234/targeted-next-generation-sequencing-in-chinese-colorectal-cancer-patients-guided-anti-egfr-treatment-and-facilitated-precision-cancer-medicine
#19
Helei Hou, Dong Liu, Chuantao Zhang, Yanxia Jiang, Guifang Lu, Na Zhou, Xiaonan Yang, Xiaoping Zhang, Zhuokun Li, Hongmei Zhu, Zhaoyang Qian, Xiaochun Zhang
Objective: Colorectal cancer (CRC) patients with both RAS and BRAF wild-type tumors determined by non-next generation sequencing (NGS) testing may still not respond due to the presence of additional mutated genes such as PIK3CA or PTEN . In this study, a broad, hybrid capture-based NGS assay was used to identify RAS, BRAF and additional targetable genetic alterations from Chinese CRC tissues. Methods: Fifty-seven cases of CRC were enrolled, and all the patients signed the informed consent...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284349/association-of-hypertension-and-treatment-outcomes-in-advanced-stage-non-small-cell-lung-cancer-patients-treated-with-bevacizumab-or-non-bevacizumab-containing-regimens
#20
Lily Z Yan, Emily V Dressler, Val R Adams
Background Studies suggest that bevacizumab-induced hypertension is prognostic of better outcomes in bevacizumab-treated patients with metastatic colorectal, HER2-negative breast, kidney, and pancreatic cancer. Few have examined this correlation in metastatic non-small cell lung cancer and evaluated whether hypertension independent of bevacizumab can improve the treatment outcomes. Objectives The primary objective was to determine the effect of hypertension on the overall response of advanced non-small cell lung cancer patients from start of the first-line chemotherapy to maintenance therapy...
April 2018: Journal of Oncology Pharmacy Practice
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