tbuckley/cabot-search huggingface dataset:
Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial
Authors: Pierre-François Laterre, Peter Pickkers, Gernot Marx, Xavier Wittebole, Ferhat Meziani, Thierry Dugernier, Vincent Huberlant, Tobias Schuerholz, Bruno François, Jean-Baptiste Lascarrou, Albertus Beishuizen, Haikel Oueslati, Damien Contou, Oscar Hoiting, Jean-Claude Lacherade, Benjamin Chousterman, Julien Pottecher, Michael Bauer, Thomas Godet, Mahir Karakas, Julie Helms, Andreas Bergmann, Jens Zimmermann, Kathleen Richter, Oliver Hartmann, Melanie Pars, Alexandre Mebazaa, Diego Castanares, Christine Collienne, Ludovic Gèrards, Phillipe Hantson, Virginie Montiel, Caroline Berghe, Marie-France Dujardin, Leslie Gielens, Suzanne Renard, Philippe Jorens, Pierre Asfar, Gaëtan Plantefève, Jacques Duranteau, Emmanuel Weiss, Constance Vuillard, Anne-Laure Fedou, Marine Goudelin, Bruno Evrard, Thomas Daix, Arnaud Desachy, Philippe Vignon, Anne-Aurore Duchambon, Ludmila Baudrillart, Paul Bourzeix, Alexandra Gay, Céline Prevost, Coralie Chalot, Isabelle Herafa, Perrine Engels, Martin Maëlle, Lila-Fariza Abeud, Laure Berton, Kamile Cerlinskaite, Nicolas Deye, Marie-Celine Fournier, Tassadit Hadjam, Alexa Hollinger, Tuija Javanainen, Clement Jourdaine, Matthieu Legrand, Badr Louadah, Arthur Neuschwander, Raphaël Clere-Jehl, Julien Demiselle, Hamid Merdji, Alexandra Monnier, Emmanuelle Mercier, Stefan Kluge, Alexander Zarbock, Arthur R. H. van Zanten, Wytze Vermeijden, Tom Dormans
Journal: Intensive Care Medicine (2021)
LBA46 Efficacy and safety of poziotinib in treatment-naïve NSCLC harboring HER2 exon 20 mutations: A multinational phase II study (ZENITH20-4)
Authors: R. Cornelissen, S. Sun, M. Wollner, M.C.C. Garassino, A. Prelaj, E.B. Haura, Z. Piotrowska, J.W. Goldman, M. Socinski, L. Dreling, G. Bhat, F. Lebel, X. Le
Journal: Annals of Oncology (2021)
Hypermutation, Mismatch Repair Deficiency, and Defining Predictors of Response to Checkpoint Blockade
Authors: Laura S. Graham, Colin C. Pritchard, Michael T. Schweizer
Journal: Clinical Cancer Research (2021)

Abstract Mutational burden is positively correlated with tumor neoantigen load and studies have demonstrated an association between high tumor mutational burden (TMB) and response to checkpoint blockade. On the basis of a phase II study, the anti-PD-1 therapy, pembrolizumab, was given FDA approval for use in any solid tumor with a high TMB (i.e., &amp;gt;10 mutations/megabase) as assessed by the FoundationOne companion diagnostic. This was an important step in expanding a potentially efficacious treatment option to patients who are likely to benefit and have limited other therapies available. Following this approval, there has been debate regarding the wide applicability of this approval and the most appropriate use of TMB as a predictive biomarker, with several studies questioning the predictive utility of TMB in this context. We discuss the scientific rationale and utility of using TMB as a tool to predict response to immunotherapy as well as address this biomarker's limitations.
1651P Phase I study of ramucirumab in combination with irinotecan plus cisplatin in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC)
Authors: T. Takahashi, K. Mori, R. Mizuno, N. Mamesaya, H. Kobayashi, S. Omori, K. Wakuda, A. Ono, T. Naito, H. Murakami, H. Kenmotsu
Journal: Annals of Oncology (2021)
534P Larotrectinib in non-CNS TRK fusion cancer patients: Outcomes by prior therapy and performance status
Authors: A. Drilon, L. Shen, C.M. van Tilburg, D.S.W. Tan, S. Kummar, J.J. Lin, F. Doz, R. McDermott, C.M. Albert, J. Berlin, S. Bielack, U.N. Lassen, M. Tahara, R. Norenberg, M. Fellous, H. Nogai, R. Xu, T.W. Laetsch, D.S. Hong
Journal: Annals of Oncology (2021)
Immunostimulatory effects of targeted thorium-227 conjugates as single agent and in combination with anti-PD-L1 therapy
Authors: Pascale Lejeune, Véronique Cruciani, Axel Berg-Larsen, Andreas Schlicker, Anne Mobergslien, Lisa Bartnitzky, Sandra Berndt, Sabine Zitzmann-Kolbe, Claudia Kamfenkel, Stefan Stargard, Stefanie Hammer, Jennifer S Jørgensen, Malene Jackerott, Carsten H Nielsen, Christoph A Schatz, Hartwig Hennekes, Jenny Karlsson, Alan S Cuthbertson, Dominik Mumberg, Urs B Hagemann
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Targeted thorium-227 conjugates (TTCs) are an emerging class of targeted alpha therapies (TATs). Their unique mode of action (MoA) is the induction of difficult-to-repair clustered DNA double-strand breaks. However, thus far, their effects on the immune system are largely unknown. Here, we investigated the immunostimulatory effects of the mesothelin-targeted thorium-227 conjugate (MSLN-TTC) in vitro and in vivo in monotherapy and in combination with an inhibitor of the immune checkpoint programmed death receptor ligand 1 (PD-L1) in immunocompetent mice. Methods The murine cell line MC38 was transfected with the human gene encoding for MSLN (hMSLN) to enable binding of the non-cross-reactive MSLN-TTC. The immunostimulatory effects of MSLN-TTC were studied in vitro on human cancer cell lines and MC38-hMSLN cells. The efficacy and MoA of MSLN-TTC were studied in vivo as monotherapy or in combination with anti-PD-L1 in MC38-hMSLN tumor-bearing immunocompetent C57BL/6 mice. Experiments were supported by RNA sequencing, flow cytometry, immunohistochemistry, mesoscale, and TaqMan PCR analyses to study the underlying immunostimulatory effects. In vivo depletion of CD8+ T cells and studies with Rag2/Il2Rg double knockout C57BL/6 mice were conducted to investigate the importance of immune cells to the efficacy of MSLN-TTC. Results MSLN-TTC treatment induced upregulation of DNA sensing pathway transcripts ( IL-6 , CCL20 , CXCL10 , and stimulator of interferon genes ( STING )-related genes) in vitro as determined by RNASeq analysis. The results, including phospho-STING activation, were confirmed on the protein level. Danger-associated molecular pattern molecules were upregulated in parallel, leading to dendritic cell (DC) activation in vitro . MSLN-TTC showed strong antitumor activity (T:C 0.38, p&lt;0.05) as a single agent in human MSLN-expressing MC38 tumor-bearing immunocompetent mice. Combining MSLN-TTC with anti-PD-L1 further enhanced the efficacy (T:C 0.08, p&lt;0.001) as evidenced by the increased number of tumor-free surviving animals. MSLN-TTC monotherapy caused migration of CD103+ cDC1 DCs and infiltration of CD8+ T cells into tumors, which was enhanced on combination with anti-PD-L1. Intriguingly, CD8+ T-cell depletion decreased antitumor efficacy. Conclusions These in vitro and in vivo data on MSLN-TTC demonstrate that the MoA of TTCs involves activation of the immune system. The findings are of relevance for other targeted radiotherapies and may guide clinical combination strategies.
961MO Safety, efficacy, immunogenicity of arenavirus-based vectors HB-201 and HB-202 in patients with HPV16+ cancers
Authors: M.R. Posner, A.L. Ho, J. Niu, L. Nabell, R.S. Leidner, J. Nieva, D.L. Richardson, A.T. Pearson, D. Wang, K. Chung, D.R. Adkins, A. Pimentel, S. Wong, C. Lacobucci, X. Qing, K. Katchar, K. Schlienger, I. Matushansky, S. Fu, D.G. Pfister
Journal: Annals of Oncology (2021)
915P Carboplatin in combination with three weekly paclitaxel as first line therapy in patients with recurrent/metastatic head and neck cancers: A regional cancer center experience
Authors: P.N. Babbar, R. Antapura Haleshappa, L. Dasappa, L.A. Jacob, S.M. Babu, L. Kadaburu Nagendrappa, R. Lakkavalli Krishnappa, S.S. Saldanha
Journal: Annals of Oncology (2021)
842P Secreted factors determine resistance to idelalisib in splenic marginal zone lymphoma (MZL) models
Authors: A.J. Arribas, S. Napoli, L. Cascione, G. Sartori, E. Gaudio, C. Tarantelli, A.A. Mensah, F. Spriano, A. Zucchetto, F.M. Rossi, A. Rinaldi, S. Jovic, A. Stathis, G. Stussi, V. Gattei, J.R. Brown, M. Esteller, E. Zucca, D. Rossi, F. Bertoni
Journal: Annals of Oncology (2021)
Partners in crime: The Lewis Y antigen and fucosyltransferase IV in Helicobacter pylori-induced gastric cancer
Authors: Faisal Aziz, Imran Khan, Shruti Shukla, Debasish Kumar Dey, Qiu Yan, Abhijit Chakraborty, Hisae Yoshitomi, Seung-Kyu Hwang, Sonam Sonwal, Hoomin Lee, Yuvaraj Haldorai, Jianbo Xiao, Yun Suk Huh, Vivek K. Bajpai, Young-Kyu Han
Journal: Pharmacology & Therapeutics (2021)
729P Adoptive T-cell therapy during chemotherapy with or without peginterferon-α (IFNα) in patients with platinum sensitive recurrent epithelial ovarian cancer (EOC)
Authors: J.R. Kroep, M. Visser, L. van der Minne, L. de Bruin, I. Roozen, P. Meij, S. van der Burg, E. Verdergaal
Journal: Annals of Oncology (2021)
Virus‐like particles displaying recombinant Der p 1 zymogen to optimize IgG blocking antibody response
Authors: Sirikarn Jitthamstaporn, Adam F. Sander, Alain Jacquet
Journal: Allergy (2021)

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708P PD-L1 as a predictor of survival in patients with metastatic urothelial carcinoma (mUC) from the phase III DANUBE trial of durvalumab (D) or durvalumab plus tremelimumab (D+T) versus standard of care chemotherapy (SoC)
Authors: J. Bellmunt, T.B. Powles, M.S. van der Heijden, M.D. Galsky, P. He, Z. Wang, F. Xiao, F. Jones, M. Scott, J. Walker, N. Angra, A. Gupta, A. Drakaki, G. Kimura, A. Mizokami, S. Wildsmith
Journal: Annals of Oncology (2021)
117O Survival after neoadjuvant therapy with trastuzumab-lapatinib and chemotherapy in patients with HER2-positive early breast cancer: A meta-analysis of randomised trials
Authors: V. Guarneri, G. Griguolo, F. Miglietta, P.F. Conte, M.V. Dieci, F. Girardi
Journal: Annals of Oncology (2021)
14P Preclinical evaluation of intermittent dosing regimens on antitumor and PD activity of SY-5609, a potent and selective oral CDK7 inhibitor, in ovarian cancer xenografts
Authors: L. Johannessen, W. Dworakowski, P. Sawant, N. Ke, A. Lefkovith, A. D'Ippolito, M. Eaton, S.H. Henry, G. Hodgson
Journal: Annals of Oncology (2021)
1857P Choose health, oncological patients centered exercise (CHOiCE): Preliminary findings of a pilot randomized controlled trial
Authors: A. Avancini, G. Scrivano, D. Tregnago, I. Trestini, S.T. Riva, L. Belluomini, J. Menis, M. Valentini, F. Leone, M. Milella, M. Lanza, S. Pilotto
Journal: Annals of Oncology (2021)
mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy
Authors: Karl P. Schlingmann, François Jouret, Kuang Shen, Anukrati Nigam, Francisco J. Arjona, Claudia Dafinger, Pascal Houillier, Deborah P. Jones, Felix Kleinerüschkamp, Jun Oh, Nathalie Godefroid, Mehmet Eltan, Tülay Güran, Stéphane Burtey, Marie-Christine Parotte, Jens König, Alina Braun, Caro Bos, Maria Ibars Serra, Holger Rehmann, Fried J.T. Zwartkruis, Kirsten Y. Renkema, Karin Klingel, Eric Schulze-Bahr, Bernhard Schermer, Carsten Bergmann, Janine Altmüller, Holger Thiele, Bodo B. Beck, Karin Dahan, David Sabatini, Max C. Liebau, Rosa Vargas-Poussou, Nine V.A.M. Knoers, Martin Konrad, Jeroen H.F. de Baaij
Journal: Journal of the American Society of Nephrology (2021)

Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all patients with tubulopathy lack a genetic diagnosis.We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent in vitro functional analyses of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase).In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by RRAGD, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro.Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.
Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes
Authors: Wantao Wu, Yihan Liu, Shan Zeng, Ying Han, Hong Shen
Journal: Journal of Hematology & Oncology (2021)

Abstract In this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis.
PAM-repeat associations and spacer selection preferences in single and co-occurring CRISPR-Cas systems
Authors: Jochem N. A. Vink, Jan H. L. Baijens, Stan J. J. Brouns
Journal: Genome biology (2021)

The adaptive CRISPR-Cas immune system stores sequences from past invaders as spacers in CRISPR arrays and thereby provides direct evidence that links invaders to hosts. Mapping CRISPR spacers has revealed many aspects of CRISPR-Cas biology, including target requirements such as the protospacer adjacent motif (PAM). However, studies have so far been limited by a low number of mapped spacers in the database.By using vast metagenomic sequence databases, we map approximately one-third of more than 200,000 unique CRISPR spacers from a variety of microbes and derive a catalog of more than two hundred unique PAM sequences associated with specific CRISPR-Cas subtypes. These PAMs are further used to correctly assign the orientation of CRISPR arrays, revealing conserved patterns between the last nucleotides of the CRISPR repeat and PAM. We could also deduce CRISPR-Cas subtype-specific preferences for targeting either template or coding strand of open reading frames. While some DNA-targeting systems (type I-E and type II systems) prefer the template strand and avoid mRNA, other DNA- and RNA-targeting systems (types I-A and I-B and type III systems) prefer the coding strand and mRNA. In addition, we find large-scale evidence that both CRISPR-Cas adaptation machinery and CRISPR arrays are shared between different CRISPR-Cas systems. This could lead to simultaneous DNA and RNA targeting of invaders, which may be effective at combating mobile genetic invaders.This study has broad implications for our understanding of how CRISPR-Cas systems work in a wide range of organisms for which only the genome sequence is known.
Implementation of a complex bone and joint infection phage therapy centre in France: lessons to be learned after 4 years' experience
Authors: Tristan Ferry, Camille Kolenda, Thomas Briot, Sébastien Lustig, Gilles Leboucher, Frédéric Laurent, Tristan Ferry, Florent Valour, Thomas Perpoint, Florence Ader, Sandrine Roux, Agathe Becker, Claire Triffault-Fillit, Anne Conrad, Cécile Pouderoux, Pierre Chauvelot, Paul Chabert, Johanna Lippman, Evelyne Braun, Sébastien Lustig, Elvire Servien, Cécile Batailler, Stanislas Gunst, Axel Schmidt, Eliott Sappey-Marinier, Quentin Ode, Michel-Henry Fessy, Anthony Viste, Jean-Luc Besse, Philippe Chaudier, Lucie Louboutin, Adrien Van Haecke, Marcelle Mercier, Vincent Belgaid, Aram Gazarian, Arnaud Walch, Antoine Bertani, Frédéric Rongieras, Sébastien Martres, Franck Trouillet, Cédric Barrey, Ali Mojallal, Sophie Brosset, Camille Hanriat, Hélène Person, Philippe Céruse, Carine Fuchsmann, Arnaud Gleizal, Frédéric Aubrun, Mikhail Dziadzko, Caroline Macabéo, Dana Patrascu, Frédéric Laurent, Laetitia Beraud, Tiphaine Roussel-Gaillard, Céline Dupieux, Camille Kolenda, Jérôme Josse, Fabien Craighero, Loic Boussel, Jean-Baptiste Pialat, Isabelle Morelec, Michel Tod, Marie-Claude Gagnieu, Sylvain Goutelle, Eugénie Mabrut, Tristan Ferry, Frédéric Laurent, Mathieu Medina, Camille Kolenda, Floriane Laumay, Melanie Bonhomme, Leslie Blazere, Tiphaine Legendre, Eline Terrazzoni, Fabrice Pirot, Camille Merienne, Samira Filali, Benjamine Lapras, Gilles Leboucher, Thomas Briot
Journal: Clinical Microbiology and Infection (2021)
1439TiP A randomized, double-blinded, placebo-controlled phase III trial of HX008 plus irinotecan as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma
Authors: J. Huang, S. Luo, P. Chen, Y. Pan, Z. Zhuang, B. Liu, Y. Ling, J. Zhang, Q. Fan, H. Wang, R. Lin, H. Zhong, Z. Chen, S. Li, J. Lv, B. Cao, L. Zhao, Y. Yang, J. Tong, S. Cang
Journal: Annals of Oncology (2021)
94P ESCAT ranking of genomic alterations collected in the Italian Registry of Actionable Mutations
Authors: R. Esposito Abate, A. De Luca, S. Novello, G. Curigliano, P. Marchetti, G. Fasola, P. Conte, M. Milella, G. Pruneri, L.G. Frassineti, C. Cremolini, C. Gridelli, V. Adamo, R. Berardi, L. Antonuzzo, A. Russo, C. Tondini, A. Morabito, C. Pinto, N. Normanno
Journal: Annals of Oncology (2021)
HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions
Authors: Elspeth A. Bruford, Cristina R. Antonescu, Andrew J. Carroll, Arul Chinnaiyan, Ian A. Cree, Nicholas C. P. Cross, Raymond Dalgleish, Robert Peter Gale, Christine J. Harrison, Rosalind J. Hastings, Jean-Loup Huret, Bertil Johansson, Michelle Le Beau, Cristina Mecucci, Fredrik Mertens, Roel Verhaak, Felix Mitelman
Journal: Leukemia (2021)

Gene fusions have been discussed in the scientific literature since they were first detected in cancer cells in the early 1980s. There is currently no standardized way to denote the genes involved in fusions, but in the majority of publications the gene symbols in question are listed either separated by a hyphen (-) or by a forward slash (/). Both types of designation suffer from important shortcomings. HGNC has worked with the scientific community to determine a new, instantly recognizable and unique separator-a double colon (::)-to be used in the description of fusion genes, and advocates its usage in all databases and articles describing gene fusions.
Product-specific COVID-19 vaccine effectiveness against secondary infection in close contacts, Navarre, Spain, April to August 2021
Authors: Iván Martínez-Baz, Camino Trobajo-Sanmartín, Ana Miqueleiz, Marcela Guevara, Miguel Fernández-Huerta, Cristina Burgui, Itziar Casado, María Eugenia Portillo, Ana Navascués, Carmen Ezpeleta, Jesús Castilla
Journal: Eurosurveillance (2021)

COVID-19 vaccine effectiveness by product (two doses Comirnaty, Spikevax or Vaxzevria and one of Janssen), against infection ranged from 50% (95% CI: 42 to 57) for Janssen to 86% (70 to 93) for Vaxzevria-Comirnaty combination; among ≥ 60 year-olds, from 17% (-26 to 45) for Janssen to 68% (48 to 80) for Spikevax; and against hospitalisation from 74% (43 to 88) for Janssen to > 90% for other products. Two doses of vaccine were highly effective against hospitalisation, but suboptimal for infection control.
ラパログ療法を越える:mTORC1とmTORC2のATP競合的および特異的阻害因子WYE-125132の前臨床薬理と抗腫瘍活性
Authors: Yu Ker, Shi Celine, Toral-Barza Lourdes, Lucas Judy, Shor Boris, Kim Jae Eun, Zhang Wei-Guo, Mahoney Robert, Gaydos Christine, Tardio LuAnna, Kim Sung Kyoo, Conant Roger, Curran Kevin, Kaplan Joshua, Verheijen Jeroen, Ayral-Kaloustian Semiramis, S Mansour Tarek, T Abraham Robert, Zask Arie, J Gibbons James
Journal: Cancer Research (2010)
Navigating from SARS-CoV-2 elimination to endemicity in Australia, Hong Kong, New Zealand, and Singapore
Authors: Chuan De Foo, Karen A Grépin, Alex R Cook, Li Yang Hsu, Michael Bartos, Sudhvir Singh, Nima Asgari, Yik Ying Teo, David L Heymann, Helena Legido-Quigley
Journal: The Lancet (2021)
Comparative genomic analysis of esophageal squamous cell carcinoma and adenocarcinoma: New opportunities towards molecularly targeted therapy
Authors: Xu Zhang, Yuxiang Wang, Linghua Meng
Journal: Acta Pharmaceutica Sinica B (2021)

Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two major subtypes of esophageal cancer. ESCC predominantly affects African and Asian populations, which is closely related to chronic smoking and alcohol consumption. EAC typically arises in Barrett's esophagus with a predilection for Western countries. While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer, molecularly targeted therapy is still at the early stages. With the development of large-scale next-generation sequencing, various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied. Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer. In this review, we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer. Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed.