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Overcoming Cancers Resistant to Her-2 Antibodies

Overcoming Cancers Resistant to Her-2 Antibodies
A Book

by Benjamin Bonavida

  • Publisher : Sensitizing Agents for Cancer
  • Release : 2019-12-15
  • Pages : 250
  • ISBN : 9780128164082
  • Language : En, Es, Fr & De
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Overcoming Cancers Resistant to HER-2 Antibodies provides general updated information on the resistance of various human cancers to anti-HER2 therapeutic antibodies. It also discusses the description of various sensitizing agents that can reverse resistance when used in combination with anti-HER2 antibodies.There have been a lot of reports in which the treatment with anti-HER2 antibodies for various cancers has resulted in clinical responses; however, there have been also subsets of cancer patients who did not respond initially, and several responding patients developed resistance following treatments. Therefore, the use of various immunosensitizing agents to reverse resistance has been considered and this book discusses each of them in depth, such as Lapatinib, Ganetespib, Paclitaxel, Celecoxib, Emantasine, Liposomal Doxorubicin, and Kinase Inhibitors. This book is a valuable source for cancer researchers, oncologists, pharmacologists and different members of biomedical field interested in fighting cancer resistance to HER-2 antibodies. Provides a general summary of various sensitizing agents that can work effectively when used in combination with anti-HER2 antibodies to reverse resistance Offers potential underlying mechanisms by which the cancer cells are either inherently resistant or become unresponsive to antibody treatment Discusses how to develop new targeted agents to underlie resistance in order to expand research on this field

Current Applications for Overcoming Resistance to Targeted Therapies

Current Applications for Overcoming Resistance to Targeted Therapies
A Book

by Myron R. Szewczuk,Bessi Qorri,Manpreet Sambi

  • Publisher : Springer
  • Release : 2019-07-15
  • Pages : 320
  • ISBN : 303021477X
  • Language : En, Es, Fr & De
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Targeted therapies were initially developed to exploit the upregulation and dependence on key oncogenic pathways critical to cancer progression. Additionally, they also presented as a method to overcome chemoresistance by supplementing conventional therapeutic regimens with targeted therapies. However, the development of resistance to these combinatorial approaches has led to the reassessment of currently available therapeutic options to overcome resistance to targeted therapy. This book aims to provide an update on the advancements in the therapeutic arms race between cancer, clinicians and scientists alike to overcome resistance to targeted therapies. Subject experts provide a comprehensive overview of the challenges and solutions to resistance to several conventional targeted therapies in addition to providing a discussion on broad topics including targeting components of the tumor microenvironment, emerging therapeutic options, and novel areas to be explored concerning nanotechnology and the epigenome.

Resistance to Immunotherapeutic Antibodies in Cancer

Resistance to Immunotherapeutic Antibodies in Cancer
Strategies to Overcome Resistance

by Benjamin Bonavida

  • Publisher : Springer Science & Business Media
  • Release : 2013-08-04
  • Pages : 202
  • ISBN : 1461476542
  • Language : En, Es, Fr & De
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​​​​The traditional approaches to treat various cancers include chemotherapy, radiation and/or hormonal therapy. While these therapies continue to be effective in large part, they are not selective and highly toxic. There have been encouraging results in alternative therapeutic approach called antibody-mediated anti-cancer therapy, which is less toxic, more selective, and can also reverse drug/radiation resistance. Monoclonal antibodies or mAbs can be used to destroy malignant tumor cells and prevent tumor growth by blocking specific cell receptors. mAbs can bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell. The book covers the common and unique features of mAbs agains various cancer, gives the latest developments on the molecular, biochemical and genetic mechanisms of resistance by various mAbs, as well as discuss novel mAbs to overcome resistance.

Overcoming Ovarian Cancer Chemoresistance

Overcoming Ovarian Cancer Chemoresistance
A Book

by Goli Samimi,Christina Annunziata

  • Publisher : Academic Press
  • Release : 2020-11-06
  • Pages : 188
  • ISBN : 0128198419
  • Language : En, Es, Fr & De
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Overcoming Ovarian Cancer Chemoresistance presents non-overlapping review chapters that discuss the state of the field in overcoming chemoresistance of ovarian cancer and treatment options before and following recurrence, considering the genetic makeup of the ovarian cancer patient and her tumor. With the uptake of both germline and somatic gene testing, clinicians can obtain a more comprehensive understanding of ovarian tumors and this book provides information to link the genetic makeup of a tumor (or patient) with the best available treatment. The book discusses topics such as strategies to fight chemo-resistance in ovarian cancer, circulating DNA as a monitor of response, BRCA mutations, ovarian cancer stem cells, immunotherapy and vaccines. Additionally, it brings a list of promising agents at clinical and pre-clinical stage that will impact the treatment in the near future. This book is a valuable source for cancer researchers, oncologists and several members of biomedical field who need to understand how to battle chemoresistance in ovarian cancer. Provides a comprehensive view of both biological and genetic determinants of resistance, as well as technical approaches to monitor response Discusses genetic reversions as a unique alteration and a new field of study Includes a chapter on upcoming and promising agents that are in the pre-clinical and early clinical space, to set the stage for future directions in the field

Translational Research in Breast Cancer

Translational Research in Breast Cancer
A Book

by Dong-Young Noh

  • Publisher : Springer Nature
  • Release : 2021
  • Pages : 329
  • ISBN : 9813296208
  • Language : En, Es, Fr & De
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Monoclonal Antibodies—Advances in Research and Application: 2012 Edition

Monoclonal Antibodies—Advances in Research and Application: 2012 Edition
A Book

by Anonim

  • Publisher : ScholarlyEditions
  • Release : 2012-12-26
  • Pages : 105
  • ISBN : 148160516X
  • Language : En, Es, Fr & De
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Monoclonal Antibodies—Advances in Research and Application: 2012 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Monoclonal Antibodies. The editors have built Monoclonal Antibodies—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Monoclonal Antibodies in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Monoclonal Antibodies—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

Cancer Cell Signaling

Cancer Cell Signaling
Targeting Signaling Pathways Toward Therapeutic Approaches to Cancer

by Kasirajan Ayyanathan

  • Publisher : CRC Press
  • Release : 2014-06-20
  • Pages : 410
  • ISBN : 1482299453
  • Language : En, Es, Fr & De
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This title includes a number of Open Access chapters. Cell signaling is a field that studies how cells communicate to control basic activities and respond to their environment. When looking specifically at cancer cells, researchers can gain a better understanding of cancer on a cellular level, an understanding that may have implications for developing new treatments. The current volume provides an overview of the field and how various cell biology techniques are used to better understand cancer on a cellular level. This easily accessible reference volume offers a comprehensive look at the field of cancer cell signaling. Edited by a researcher from Florida Atlantic University, Cancer Cell Signaling: Targeting Signaling Pathways Towards Therapeutic Approaches to Cancer is an authoritative and easy-to-use reference.

Investigating Novel Therapies for Breast Cancers Resistant to Trastuzumab

Investigating Novel Therapies for Breast Cancers Resistant to Trastuzumab
A Book

by Banujan Balachandran

  • Publisher : Unknown Publisher
  • Release : 2013
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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"Approximately 20% of all metastatic breast cancers overexpress the HER-2 receptor, a cell surface-bound receptor tyrosine kinase upstream of crucial proliferation and cell survival pathways. Trastuzumab, a humanized monoclonal antibody binding to the extracellular domain of HER-2, has proven to be a beneficial treatment for patients diagnosed as HER-2+ but continues to have limitations. With low response rates for patients when administered alone and for patients having received prior chemotherapy, the true potential of trastuzumab seems to arrive only through combination therapies. However, the majority of advanced HER-2 positive breast cancer patients still develop resistance to the therapy by the end of the first year or present de novo resistance. For this reason, it is important to continue to investigate therapies to give in combination with trastuzumab to improve progression-free survival and overall survival in this clinical setting. Two Phase II Astra Zeneca compounds: AZD0530, a dual Src and Abl kinase inhibitor and AZD8931, a pan-erbb tyrosine kinase inhibitor abrogating EGFR-, HER-2-, and HER-3-mediated signaling were explored in this context using established trastuzumab-naïve and trastuzumab-resistant cell lines. AZD0530 was not effective when administered alone and any combinations with trastuzumab showed positive responses only in those models in which some form of response to AZD0530 alone had been seen. Clinically-relevant responses to AZD8931 were seen in all cell lines tested and for this reason a head-to-head comparison was carried out with lapatinib, the FDA-approved therapy for patients progressing on trastuzumab. AZD8931 alone and in combination with trastuzumab worked effectively to stop proliferation and induce cell death in both trastuzumab-naïve and trastuzumab-resistant cell lines at clinically relevant doses. AZD8931 had similar activity to lapatinib in the SKBR3-based ER-negative cell lines, but was less active in the BT474-based ER-positive cell lines. From this study, it appears AZD8931 is a therapeutic candidate for overcoming trastuzumab resistance but further investigation is required, before translation into the clinical setting, including the use of animal models of trastuzumab-resistance, specifically in the ER-negative subtype." --

Breast Cancer

Breast Cancer
Carcinogenesis, Cell Growth and Signalling Pathways

by Mehmet Gunduz,Esra Gunduz

  • Publisher : BoD – Books on Demand
  • Release : 2011-11-30
  • Pages : 746
  • ISBN : 953307714X
  • Language : En, Es, Fr & De
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Cancer is the leading cause of death in most countries and its consequences result in huge economic, social and psychological burden. Breast cancer is the most frequently diagnosed cancer type and the leading cause of cancer death among females. In this book, we discussed various aspects of breast cancer carcinogenesis from clinics to its hormone-based as well as genetic-based etiologies for this deadly cancer. We hope that this book will contribute to the development of novel diagnostic as well as therapeutic approaches.

Handbook of HER2-targeted agents in breast cancer

Handbook of HER2-targeted agents in breast cancer
A Book

by Ricardo H Alvarez,Javier Cortés,Leticia Mattos-Arruda,Mary Falzon,Angelica Fasolo,Michael Gandy,Luca Gianni,Nadia Harbeck,Martine Piccart,Stefania Zambelli,Dimitrios Zardavas

  • Publisher : Springer
  • Release : 2014-05-28
  • Pages : 96
  • ISBN : 1907673946
  • Language : En, Es, Fr & De
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​Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for nearly a quarter of the total new cancer cases each year. Of these cases, approximately 15–25% overexpress HER2, a transmembrane RTK kinase that is associated with aggressive tumor growth and poor outcomes. However, in the past decade, survival rates of patients with HER-positive breast cancer have significantly improved due to increased screening, HER2 testing, and breakthrough HER2-targeted drug therapies. Handbook of HER2-Targeted Agents in Breast Cancer provides oncologists, primary care physicians, trainees and other healthcare providers with a concise, accessible, and up-to-date survey of the field, including a review of our current understanding of the biology of the HER2 pathway and the rationale for targeting it in early-stage and advanced breast cancer, an overview of HER2-testing, and evidence-based discussions of available HER2-targeted regimens in the adjuvant and metastatic settings.

Targeted Cancer Therapies, From Small Molecules to Antibodies

Targeted Cancer Therapies, From Small Molecules to Antibodies
A Book

by Zhe-Sheng Chen,Jian-ye Zhang,Yunkai Zhang,Yan-yan Yan

  • Publisher : Frontiers Media SA
  • Release : 2020-07-22
  • Pages : 329
  • ISBN : 2889638847
  • Language : En, Es, Fr & De
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PDK-1/Akt Pathway as Targets for Chemosensitizing Effects

PDK-1/Akt Pathway as Targets for Chemosensitizing Effects
A Book

by Ping-Hui Tseng

  • Publisher : Unknown Publisher
  • Release : 2005
  • Pages : 116
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Abstract: Cancer is the leading causes of human deaths all over the world. The growing understanding in cancer biology provides the researchers to develop molecularly targeted therapeutic strategies. However, the toxicity and resistance limit the applications for molecularly targeted agents. Here, we proposed that inhibiting PI3K/PDK-1/Akt signaling pathway, which is critical in controlling cell survival and proliferation, is able to enhance the therapeutic effects and overcome resistance of the current used molecularly targeted drugs. Imatinib (STI571; Gleevec), a selective bcr-abl tyrosine kinase inhibitor, is approved to treat patients with chronic myelogenous leukemia (CML). However, patients in more advanced phases of CML frequently develop resistance to the treatment. Mutations within the kinase domain for the binding of imatininb attributes as one of the major imatinib-resistant mechanisms. The effects of imatinib each alone and in combination with OSU-03012, a novel celecoxib-derived PDK-1 inhibitor, was evaluated in a panel of Bcr-Abl positive Ba/F3 cell lines without or with mutations. The IC50 values for OSU-03012 alone were comparable, while the sensitivities to imatinib alone were differed. The combination treatment, however, caused a synergistic enhancement of apoptosis in these cells, including those that are resistant to imatinib. HER2/neu is frequently over-expressed in breast cancers that are characterized by aggressive tumor progression and resistant to current therapies. The effects of trastuzumab (Herceptin), a monoclonal antibody targeting to HER2/neu, alone and in combination with OSU-03012 were evaluated in a panel of breast cancer cell lines. The IC50 values for OSU-03012 alone in four cell lines were comparable, while the sensitivities to trastuzumab alone were mainly dependent on the HER2/neu expression level or resistant phenotypes. The combination treatments, however, caused a synergistic enhancement of anti-proliferation in HER2/neu positive cell lines, including SKBR3/IGF-IR, as a resistant phenotype, that responded poorly to trastuzumab. These results demonstrate the potential clinical value of a therapeutic strategy to sensitize cancer cells to molecularly targeted drugs by co-targeting PDK-1/Akt signaling. More importantly, the co-treatments are able to overcome drug resistance.

Small Molecules in Oncology

Small Molecules in Oncology
A Book

by Uwe M. Martens

  • Publisher : Springer
  • Release : 2018-08-01
  • Pages : 276
  • ISBN : 3319914421
  • Language : En, Es, Fr & De
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This book, written by respected experts, discusses in detail the latest developments in targeted oncology therapy using small molecules. It covers a wide range of small molecules, including tyrosine kinase inhibitors, mTOR, MEK, PARP, and multikinase inhibitors, as well as cell cycle and NTRK interacting agents. For each molecule, aspects such as the chemical structure, mechanism of action, drug targets, drug interactions, preclinical studies, clinical trials, treatment applications, and toxicity are discussed. Extensive research into the molecular mechanisms of cancer has heralded a new age of targeted therapy. The field of personalized cancer therapy is now growing rapidly, and the advances being made will mean significant changes in the treatment algorithms for cancer patients. Numerous novel targets that are crucial for the survival of cancer cells can be attacked by small molecules such as protein tyrosine kinase inhibitors. This book is the third edition of Small Molecules in Oncology, but has now been divided into two volumes, with the other volume focusing specifically on small molecules in hematology.

Cancer Drug Discovery

Cancer Drug Discovery
Science and History

by Kyu-Won Kim,Jae Kyung Roh,Hee-Jun Wee,Chan Kim

  • Publisher : Springer
  • Release : 2016-11-14
  • Pages : 276
  • ISBN : 9402408444
  • Language : En, Es, Fr & De
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The reader will discover a comprehensive and multifaceted overview of the history of the development of anticancer drugs deeply influenced by the cell concept of cancer and future directions for the development of new anticancer drugs. First, this book documents the scientific progress in biological science over the last 70 years and the influence this progress had in cancer research. Summaries and charts of important discoveries complete this overview. Furthermore, this book outlines the process of anticancer drug development with a focus on the characteristic drug groups of each era, related to advancements of chemistry and biological sciences. This book also provides brief mechanism of action of drugs, illustrated by comprehensive timelines and conceptual cartoons. This book finally sums up the limitations of the current anticancer drug development and seeks new directions for anticancer drug discovery, considering under the systemic view of cancer.

Nanostructures for Cancer Therapy

Nanostructures for Cancer Therapy
A Book

by Alexandru Mihai Grumezescu,Anton Ficai

  • Publisher : Elsevier
  • Release : 2017-04-11
  • Pages : 920
  • ISBN : 0323461506
  • Language : En, Es, Fr & De
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Nanostructures for Cancer Therapy discusses the available preclinical and clinical nanoparticle technology platforms and their impact on cancer therapy, including current trends and developments in the use of nanostructured materials in chemotherapy and chemotherapeutics. In particular, coverage is given to the applications of gold nanoparticles and quantum dots in cancer therapies. In addition to the multifunctional nanomaterials involved in the treatment of cancer, other topics covered include nanocomposites that can target tumoral cells and the release of antitumoral therapeutic agents. The book is an up-to-date overview that covers the inorganic and organic nanostructures involved in the diagnostics and treatment of cancer. Provides an examination of nanoparticle delivery systems for cancer treatment, illustrating how the use of nanotechnology can help provide more effective chemotherapeutic treatments Examines, in detail, the different types of nanomaterials used in cancer therapy, also explaining the effect of each Provides a cogent overview of recent developments in the use of nanostructured materials in chemotherapeutics, allowing readers to quickly familiarize themselves with this area

Innovations for Next-Generation Antibody-Drug Conjugates

Innovations for Next-Generation Antibody-Drug Conjugates
A Book

by Marc Damelin

  • Publisher : Springer
  • Release : 2018-05-29
  • Pages : 357
  • ISBN : 3319781545
  • Language : En, Es, Fr & De
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Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.

Breast Disease

Breast Disease
Management and Therapies

by Adnan Aydiner,Abdullah İgci,Atilla Soran

  • Publisher : Springer
  • Release : 2016-05-09
  • Pages : 934
  • ISBN : 331926012X
  • Language : En, Es, Fr & De
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This second volume of the handbook on breast disease provides a comprehensive overview of its clinical management and current therapies. It brings readers up to speed with the latest guidelines and therapeutic regimens in breast cancer and provides and in-depth account of current and new therapeutic approaches. Divided in themed parts, the book examines invasive breast cancer, pre-operative systemic therapy surgical management and recurrence among others, thus providing an in-depth account of breast cancer at the clinical stage. Among the themed parts are a section dedicated to special therapeutic problems, such as breast cancer in older women, Paget’s disease and phyllodes tumors, and a section on supportive and follow-up care. By adopting a multidisciplinary approach to breast cancer, this book is a must- have for breast cancer practitioners. With a high number of colored illustrations and edited by highly experienced clinicians, this work enables readers to gain an interdisciplinary perspective on breast diseases. Contributions from an international team of experts present invaluable insight into clinical practice across different settings. Covering both theoretical and practical aspects of breast cancer, this is a highly informative and carefully presented book which will appeal to an international audience of medical, radiation and surgical oncologists.

Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance

Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance
A Book

by Andrew Freywald,Franco Vizeacoumar

  • Publisher : Academic Press
  • Release : 2020-12-04
  • Pages : 308
  • ISBN : 0128213116
  • Language : En, Es, Fr & De
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Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance, Volume 12, discusses new approaches that are being undertaken to counteract tumor plasticity, understand and tackle the interactions with the microenvironment, and disrupt the rewiring of malignant cells or bypass biological mechanism of resistance by using targeted radionuclide therapies. This book provides a unique opportunity to the reader to understand the fundamental causes of drug resistance and how different approaches are applied. It is a one-stop-shop to understand why it is so difficult to treat cancer, and why only a very few patients respond to therapy and a significant portion develop resistance. Despite a rapid development of more effective anti-cancer drugs and combination therapies, cancer remains the leading cause of lethality in the developed world. The main reason for this is the ability of heterogeneous subpopulations of tumor cells interacting with constantly evolving tumor microenvironment to resist elimination and eventually, trigger cancer relapse. In this book, experts review current concepts explaining molecular and biological mechanisms of cancer drug resistance and discussing advancing approaches for overcoming these therapeutic challenges. Provides the most updated knowledge on the mechanisms of cancer drug resistance and the emerging therapeutic approaches reviewed by experts in the field Brings detailed analyses of most important recently reported developments related to drug resistance and their relevance to overcoming it in cancer patients Discusses in-depth molecular mechanisms and novel concepts of cancer resistance to conventional and advanced therapies

Molecular Testing in Cancer

Molecular Testing in Cancer
A Book

by George M. Yousef,Serge Jothy

  • Publisher : Springer Science & Business
  • Release : 2014-04-21
  • Pages : 442
  • ISBN : 1489980504
  • Language : En, Es, Fr & De
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Molecular Testing in Cancer provides a state of the art review of clinically relevant molecular pathology in cancer. The book provides a brief, easy to read review of commonly employed diagnostic molecular techniques including recently developed "next generation" analytic tools, and offers a system-based run-through of the utility of molecular testing in individual cancer types, as well as reviewing current markers in cancer diagnosis, prognosis, and management. The volume also provides a prospective for the future which includes recently characterized and emerging biomarkers. Written by experts in the field, Molecular Testing in Cancer serves as a useful and comprehensive resource for pathologists, hematologists, laboratory technicians and molecular scientists.

Characterization of Molecular Mechanisms of Acquired Resistance to Trastuzumab in Gastric Cancer

Characterization of Molecular Mechanisms of Acquired Resistance to Trastuzumab in Gastric Cancer
A Book

by Aïda Sampera Borràs

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 161
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The HER2 receptor is overexpressed in 7-34% of gastric cancer (GC) tumors, being a potential therapeutic target. Trastuzumab, an anti-HER2 monoclonal antibody, in combination with platinum therapy was approved in 2010 as first-line treatment for advanced GC tumors overexpressing HER2. Despite the clinical benefit of trastuzumab, development of acquired resistance to treatment limits the efficacy of trastuzumab. To study the mechanisms of trastuzumab acquired resistance we generated, upon chronic exposure to trastuzumab, a trastuzumab-resistant cell line derived from the human HER2-positive GC cell NCI-N87, hereafter named NTR2.4. The resistant phenotype of NTR2.4 cell line was associated with an increased basal activation of SRC, MAPK/ERK and PI3K/mTOR HER2 downstream pathways that persisted upon exposure to trastuzumab. Trastuzumab treatment induced a compensatory upregulation of HER3 and an increased expression of the HER family ligands EGF, AREG, HB-EGF, and NRG1 in NTR2.4 compared with the trastuzumab-sensitive NCI-N87 cell line. Ligand stimulation induced resistance to trastuzumab in NCI-N87 cells. These results were replicated in another model of trastuzumab-resistance, OTR6 cell line, suggesting an important role of HER receptor plasticity and HER family ligand in trastuzumab efficacy and resistance. Analysis of clinical samples from HER2-positive GC patients treated with trastuzumab showed higher EGF concentration in serum samples and increased EGF mRNA expression in tumor biopsies at trastuzumab progression compared with samples previous to trastuzumab treatment. Treatment with Pan-HER, a novel antibody mixture against EGFR, HER2, and HER3, was effective in both trastuzumab-sensitive and trastuzumab-resistant cell lines and also in the presence of ligands. Altogether, our results suggested that Pan-HER would be a potential candidate to overcome trastuzumab resistance in advanced GC patients.