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https://www.readbyqxmd.com/read/29234896/correction-to-multicenter-phase-ii-study-of-trastuzumab-plus-s-1-alone-in-elderly-patients-with-her2-positive-advanced-gastric-cancer-jaccro-gc%C3%A2-06
#1
Yutaka Kimura, Masashi Fujii, Toshiki Masuishi, Kazuhiro Nishikawa, Chikara Kunisaki, Satoshi Matsusaka, Yoshihiko Segawa, Masato Nakamura, Kinro Sasaki, Narutoshi Nagao, Yukimasa Hatachi, Yasuhiro Yuasa, Shinya Asami, Masahiro Takeuchi, Hiroshi Furukawa, Toshifusa Nakajima
The correct name of the twelfth author should be ''Yasuhiro Yuasa", and not ''Yasuhiko Yuasa'' as given in the original publication of the article.
December 12, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/29233896/retargeting-lentiviruses-via-spycatcher-spytag-chemistry-for-gene-delivery-into-specific-cell-types
#2
Nagarjun Kasaraneni, Ana M Chamoun-Emanuelli, Gus Wright, Zhilei Chen
We report a simple strategy for the creation of lentiviral vectors specific to any desired target cells. SpyTag is inserted into an engineered Sindbis virus envelope protein and displayed on the lentivirus surface to create Sindbis virus-SpyTag pseudoparticles (Sind-SpyTag-pp). The SpyTag serves as the covalent anchoring site for a target-cell-specific cell-binding protein (CBP) that is fused to a truncated SpyCatcher (SpyCatcherΔ). Target-cell-specific lentiviruses are created by mixing the Sind-SpyTag-pp and CBP-SpyCatcherΔ in vitro We first used a HER2-binding designed ankyrin repeat protein (DARPin...
December 12, 2017: MBio
https://www.readbyqxmd.com/read/29233824/role-for-immune-therapy-in-advanced-breast-cancer
#3
(no author information available yet)
In a phase Ib/II trial, adding the PD-1 inhibitor pembrolizumab to trastuzumab showed clinical benefit in patients with advanced HER2-positive breast cancer who had developed resistance to trastuzumab. The study also identified tumor-infiltrating lymphocyte levels as a potential biomarker of response to treatment.
December 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29232309/a-bispecific-antibody-based-on-pertuzumab-fab-has-potent-antitumor-activity
#4
Wentong Deng, Jiayu Liu, Haitao Pan, Li Li, Changhua Zhou, Xiaojuan Wang, Rui Shu, Bin Dong, Donglin Cao, Qing Li, Zhong Wang
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody...
January 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29231994/nes1-klk10-promotes-trastuzumab-resistance-via-activation-of-pi3k-akt-signaling-pathway-in-gastric-cancer
#5
Laiqin Tang, Zhiguo Long, Guangjia Feng, Xianzhi Guo, Minghua Yu
Trastuzumab, a humanized antibody targeting human epidermal growth factor receptor 2 (HER2), exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. Acquired resistance to trastuzumab remains a barrier to patient survival and the mechanisms underlying this are still not well understood. The normal epithelial cell-specific-1 (NES1) gene, also named as KLK10, is recognized as a potential therapeutic target for reversing trastuzumab resistance. The aim of this study was to explore the potential role of KLK10 in trastuzumab resistance (TR) gastric cancer cells...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29231164/lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-a%C3%A2-systematic-review%C3%A2
#6
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/29230121/leptomeningeal-disease-and-the-evolving-role-of-molecular-targeted-therapy-and-immunotherapy
#7
REVIEW
Katharine Hall Thomas, Robert A Ramirez
Background: Leptomeningeal disease (LMD) is a complication that results from solid tumor metastasis. Prognosis is extremely poor. As therapeutic options for solid tumors improve, the rate of LMD continues to increase. Until recently, treatment has been limited to radiation therapy, intrathecal chemotherapy, and systemic chemotherapy, with an overall survival of 2-3 months. Targeted molecular therapy and immunotherapies are promising new options for increasing overall survival and clinical improvement; however, optimal clinical management remains unknown...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29230119/a-potential-additional-variable-to-consider-in-the-surgical-treatment-of-ductal-carcinoma-in-situ
#8
Katherine Chaisson, Amy Rivere, Ralph Corsetti, Tova Weiss, George M Fuhrman
Background: HER2/neu is a potentially interesting variable that has been demonstrated to have a profound impact on the management of invasive breast carcinoma, and we performed this study to evaluate the differences between HER2-positive and HER2-negative ductal carcinoma in situ. The impetus for this study was our poor recruitment to the National Surgical Adjuvant Breast and Bowel Project Protocol B-43 trial that was designed to evaluate the potential role of trastuzumab in breast conservation therapy for patients with HER2-positive ductal carcinoma in situ...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29227816/the-use-of-breast-imaging-for-predicting-response-to%C3%A2-neoadjuvant-lapatinib-trastuzumab-and-their-combination-in-her2-positive-breast-cancer-results%C3%A2-from-neo-altto
#9
S Di Cosimo, C Campbell, H A Azim, G Galli, G Bregni, G Curigliano, C Criscitiello, M Izquierdo, L de la Pena, D Fumagalli, L Fein, J Vinholes, W M J Ng, M Colleoni, A Ferro, B J Naume, A Patel, J Huober, M J Piccart-Gebhart, J Baselga, E de Azambuja
AIM: To determine the value of mammography and breast ultrasound (US) in predicting outcomes in HER2 positive breast cancer patients (pts) within Neo-ALTTO trial. PATIENTS AND METHODS: Mammography and US were required at baseline, week 6 and surgery. Two independent blinded investigators reviewed the measurements and assigned the corresponding response category. Pts showing complete or partial response according to RECIST (v1.1) were classified as responders. The association between imaging response at week 6 or prior to surgery was evaluated with respect to pathological complete response (pCR) and event-free Survival (EFS)...
December 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29225726/incidence-diagnosis-and-treatment-of-cardiac-toxicity-from-trastuzumab-in-patients-with-breast-cancer
#10
Somaira Nowsheen, Paul V Viscuse, Ciara C O'Sullivan, Nicole P Sandhu, Tufia C Haddad, Anne Blaes, Jennifer Klemp, Lara Nhola, Joerg Herrmann, Kathryn J Ruddy
Purpose of review: Treatment with trastuzumab is a cornerstone of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but carries an unfortunate risk of toxicity to the cardiovascular system. Here we review recent findings on trastuzumab-associated cardiotoxicity, focusing on its incidence, diagnosis, and treatment. Recent findings: Screening with multigated acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac function prior to and during trastuzumab therapy...
September 2017: Current Breast Cancer Reports
https://www.readbyqxmd.com/read/29223479/long-term-efficacy-analysis-of-the-randomised-phase-ii-tryphaena-cardiac-safety-study-evaluating-pertuzumab-and-trastuzumab-plus-standard-neoadjuvant-anthracycline-containing-and-anthracycline-free-chemotherapy-regimens-in-patients-with-her2-positive-early
#11
Andreas Schneeweiss, Stephen Chia, Tamas Hickish, Vernon Harvey, Alexandru Eniu, Maeve Waldron-Lynch, Jennifer Eng-Wong, Sarah Kirk, Javier Cortés
BACKGROUND: We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy. METHODS: Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient...
December 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29221608/a-case-of-eruptive-disseminated-porokeratosis-in-a-cancer-patient-after-trastuzumab-and-exemestane-treatment-cancer-related-or-drug-induced-phenomenon
#12
C Mangas, V Espeli, R Blum
No abstract text is available yet for this article.
December 5, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/29217763/improved-tumor-penetration-and-single-cell-targeting-of-antibody-drug-conjugates-increases-anticancer-efficacy-and-host-survival
#13
Cornelius Cilliers, Bruna Menezes, Ian Nessler, Jennifer Linderman, Greg Thurber
Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small molecule payload and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADC is poorly understood. Here we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, co-administration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared to T-DM1 alone...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29214842/trastuzumab-emtansine-determining-its-role-in-management-of-her2-breast-cancer
#14
Deborah B Doroshow, Patricia M LoRusso
Trastuzumab emtansine is an antibody-drug conjugate comprised of the anti-HER2 monoclonal antibody trastuzumab linked to DM1 (emtansine), a potent cytotoxic maytansinoid derivative, by a stable linker. This structure results in improved tumor-directed cytotoxicity in HER2+ breast cancer with reduced systemic toxicities, particularly the cardiac toxicities associated with single agent trastuzumab. Phase III trials have demonstrated improved progression-free and overall survival in heavily pretreated patients with advanced HER2+ breast cancer, with an acceptable toxicity profile...
December 7, 2017: Future Oncology
https://www.readbyqxmd.com/read/29212784/an-oligoclonal-antibody-durably-overcomes-resistance-of-lung-cancer-to-third-generation-egfr-inhibitors
#15
Maicol Mancini, Hilah Gal, Nadège Gaborit, Luigi Mazzeo, Donatella Romaniello, Tomer Meir Salame, Moshit Lindzen, Georg Mahlknecht, Yehoshua Enuka, Dominick Ga Burton, Lee Roth, Ashish Noronha, Ilaria Marrocco, Dan Adreka, Raya Eilam Altstadter, Emilie Bousquet, Julian Downward, Antonio Maraver, Valery Krizhanovsky, Yosef Yarden
Epidermal growth factor receptor (EGFR) mutations identify patients with lung cancer who derive benefit from kinase inhibitors. However, most patients eventually develop resistance, primarily due to the T790M second-site mutation. Irreversible inhibitors (e.g., osimertinib/AZD9291) inhibit T790M-EGFR, but several mechanisms, including a third-site mutation, C797S, confer renewed resistance. We previously reported that a triple mixture of monoclonal antibodies, 3×mAbs, simultaneously targeting EGFR, HER2, and HER3, inhibits T790M-expressing tumors...
December 6, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29212525/establishing-and-characterizing-patient-derived-xenografts-using-pre-chemotherapy-percutaneous-biopsy-and-post-chemotherapy-surgical-samples-from-a-prospective-neoadjuvant-breast-cancer-study
#16
Jia Yu, Bo Qin, Ann M Moyer, Jason P Sinnwell, Kevin J Thompson, John A Copland, Laura A Marlow, James L Miller, Ping Yin, Bowen Gao, Katherine Minter-Dykhouse, Xiaojia Tang, Sarah A McLaughlin, Alvaro Moreno-Aspitia, Anthony Schweitzer, Yan Lu, Jason Hubbard, Donald W Northfelt, Richard J Gray, Katie Hunt, Amy L Conners, Vera J Suman, Krishna R Kalari, James N Ingle, Zhenkun Lou, Daniel W Visscher, Richard Weinshilboum, Judy C Boughey, Matthew P Goetz, Liewei Wang
BACKGROUND: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting...
December 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29209569/resistance-to-her2-targeted-anti-cancer-drugs-is-associated-with-immune-evasion-in-cancer-cells-and-their-derived-extracellular-vesicles
#17
Vanesa G Martinez, Sadhbh O'Neill, Josephine Salimu, Susan Breslin, Aled Clayton, John Crown, Lorraine O'Driscoll
Neuromedin U (NmU) -a neuropeptide belonging to the neuromedin family- plays a substantial role in HER2-positive breast cancer, correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients. However, the mechanism through which it exerts these effects remains unclear. To elucidate this, initially we used HER2-positive breast cancer cells stably over-expressing NmU. These cells and their released extracellular vesicles (EVs) had increased amounts of the immunosuppressive cytokine TGFβ1 and the lymphocyte activation inhibitor PD-L1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29209558/development-and-clinical-application-of-anti-her2-monoclonal-and-bispecific-antibodies-for-cancer-treatment
#18
REVIEW
Shengnan Yu, Qian Liu, Xinwei Han, Shuang Qin, Weiheng Zhao, Anping Li, Kongming Wu
HER2-targeted immunotherapy consists of monoclonal antibodies (e.g. trastuzumab, pertuzumab), bispecific antibodies (e.g. MM-111, ertumaxomab) and activated T cells armed with anti-HER2 bispecific antibody (HER2Bi-aATC). Trastuzumab is a classic drug for the treatment of HER2 positive metastatic breast cancer. The combined application of pertuzumab, trastuzumab and paclitaxel has been suggested as a standard therapy for HER2 positive advanced breast cancer. The resistance to anti-HER2 antibody has resulted in disease progression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29209523/second-line-treatments-moving-towards-an-opportunity-to-improve-survival-in-advanced-gastric-cancer
#19
REVIEW
Massimiliano Salati, Katia Di Emidio, Vittoria Tarantino, Stefano Cascinu
Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting...
2017: ESMO Open
https://www.readbyqxmd.com/read/29209315/gradual-increase-of-fc%C3%AE-riiia-cd16a-expression-and-shift-toward-ifn-%C3%AE-secretion-during-differentiation-of-cd56dim-natural-killer-cells
#20
Laurie Lajoie, Nicolas Congy-Jolivet, Armelle Bolzec, Gilles Thibault
Natural killer (NK) cell effector functions include cytotoxicity and secretion of cytokines such as interferon-γ (IFN-γ). The immature CD56bright subset of human NK cells lacks expression of FcγRIIIa/CD16a, one of the low-affinity immunoglobulin G receptors, or exhibits low-density expression (CD56brightCD16-/dim) and produces IFN-γ in response to cytokine stimulation, whereas the mature CD56dimCD16+ subset is the most cytotoxic one. A further differentiation/maturation of the latter subset according to the gradual loss of NKG2A and/or gain of KIR2DL (CD158a and CD158b) has been demonstrated and the ability to produce IFN-γ in response to activating receptor (AR) co-engagement is gradually acquired during terminal differentiation...
2017: Frontiers in Immunology
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