Sarcoma treatment in the era of molecular medicine

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Abstract

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult‐to‐treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.

Abstract

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. The current article comprehensively reviews recent advances in the molecular characterization of sarcoma subtypes, and describes novel therapeutic targets and biomarkers in this field.

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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Approaches to treat immune hot, altered and cold tumours with combination immunotherapies

Jérôme Galon, Daniela Bruni (2019)

Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Recent technological, analytical and mechanistic advances in immunology have enabled the identification of patients who are more likely to respond to immunotherapy. In this Review, we focus on defining hot, altered and cold tumours, the complexity of the tumour microenvironment, the Immunoscore and immune contexture of tumours, and we describe approaches to treat such tumours with combination immunotherapies, including checkpoint inhibitors. In the upcoming era of combination immunotherapy, it is becoming critical to understand the mechanisms responsible for hot, altered or cold immune tumours in order to boost a weak antitumour immunity. The impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.

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3D bioprinting of tissues and organs.

Sean Murphy, Anthony Atala (2014)

Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

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Author and article information

Contributors

Thomas GP Grünewald:

ORCID: https://orcid.org/0000-0003-0920-7377

t.gruenewald@dkfz-heidelberg.de

Nicola Baldini:

ORCID: https://orcid.org/0000-0003-2228-3833

nicola.baldini@ior.it

Dominique Heymann:

ORCID: https://orcid.org/0000-0001-7777-0669

dominique.heymann@univ-nantes.fr

Journal

Journal ID (nlm-ta): EMBO Mol Med

Journal ID (iso-abbrev): EMBO Mol Med

Journal ID (doi): 10.1002/(ISSN)1757-4684

Journal ID (publisher-id): EMMM

Journal ID (hwp): embomm

Title: EMBO Molecular Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1757-4676

ISSN (Electronic): 1757-4684

Publication date (Electronic): 13 October 2020

Publication date (Print): 06 November 2020

Volume: 12

Issue: 11 ( doiID: 10.1002/emmm.v12.11 )

Electronic Location Identifier: e11131

Affiliations

[ ¹ ] Max‐Eder Research Group for Pediatric Sarcoma Biology Institute of Pathology Faculty of Medicine LMU Munich Munich Germany

[ ² ] Division of Translational Pediatric Sarcoma Research German Cancer Research Center (DKFZ), Hopp Children's Cancer Center (KiTZ), German Cancer Consortium (DKTK) Heidelberg Germany

[ ³ ] Institute of Pathology Heidelberg University Hospital Heidelberg Germany

[ ⁴ ] Program in Solid Tumors and Biomarkers Foundation for the Applied Medical Research University of Navarra Pamplona Pamplona Spain

[ ⁵ ] Orthopedic Pathophysiology and Regenerative Medicine Unit IRCCS Istituto Ortopedico Rizzoli Bologna Italy

[ ⁶ ] Pediatric Soft Tissue Sarcoma Research Group German Cancer Research Center (DKFZ) Heidelberg Germany

[ ⁷ ] Department of Pediatrics and Children's Cancer Research Center (CCRC) Technische Universität München Munich Germany

[ ⁸ ] Children's Cancer Research Institute Vienna Austria

[ ⁹ ] Department of Pediatric Oncology/Hematology Charité‐Universitätsmedizin Berlin Berlin Germany

[ ¹⁰ ] Cellular Biotechnology Unit Instituto de Salud Carlos III Madrid Spain

[ ¹¹ ] Centre for Craniofacial and Regenerative Biology King's College London London UK

[ ¹² ] Department of Pediatrics University Hospital Erlangen Germany

[ ¹³ ] Division of Oncology Adhesion and Metastasis Laboratory Center for Applied Medical Research University of Navarra Pamplona Spain

[ ¹⁴ ] Institute of Biostructures and Bioimaging (IBB) Italian National Research Council (CNR) Turin Italy

[ ¹⁵ ] Department of Oncology and Metabolism University of Sheffield Sheffield UK

[ ¹⁶ ] Department of General, Visceral and Transplantation Surgery University of Heidelberg Heidelberg Germany

[ ¹⁷ ] Université de Nantes, Inserm, U1238 Nantes France

[ ¹⁸ ] Department of Pharmaceutical Technology Faculty of Pharmacy University of Coimbra Coimbra Portugal

[ ¹⁹ ] Instituto de Investigación Sanitaria del Principado de Asturias Oviedo Spain

[ ²⁰ ] CIBER en oncología (CIBERONC) Madrid Spain

[ ²¹ ] Institute of Pathology Ulm University Ulm Germany

[ ²² ] Department of Drug Design University of Groningen Groningen The Netherlands

[ ²³ ] Department of Oral and Maxillofacial Diseases University of Helsinki Helsinki Finland

[ ²⁴ ] Division of Translational Pathology Gerhard‐Domagk‐Institute of Pathology Münster University Hospital Münster Germany

[ ²⁵ ] Hospital La Paz Institute for Health Research (IdiPAZ) Madrid Spain

[ ²⁶ ] Department of Medical Oncology Radboud University Medical Center Nijmegen The Netherlands

[ ²⁷ ] Medical Center Duke University Durham NC USA

[ ²⁸ ] University Children′s Hospital Zurich – Eleonoren Foundation Kanton Zürich Zürich Switzerland

[ ²⁹ ] Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy

[ ³⁰ ] Université de Nantes Institut de Cancérologie de l'Ouest Tumor Heterogeneity and Precision Medicine Saint‐Herblain France

Author notes

[*] [* ] Corresponding author. Tel: +49 6221 42 3718; E‐mail: t.gruenewald@ 123456dkfz-heidelberg.de

Corresponding author. Tel: +39 (0) 516 366 549; E‐mail: nicola.baldini@ 123456ior.it

Corresponding author. Tel: +33 (0) 240 679 841; E‐mail: dominique.heymann@ 123456univ-nantes.fr

Author information

Thomas GP Grünewald https://orcid.org/0000-0003-0920-7377

Marta Alonso https://orcid.org/0000-0002-7520-7351

Florencia Cidre‐Aranaz https://orcid.org/0000-0002-0246-7179

Rene Rodriguez https://orcid.org/0000-0002-0768-7306

Marcel Trautmann https://orcid.org/0000-0002-5842-1196

Nicola Baldini https://orcid.org/0000-0003-2228-3833

Dominique Heymann https://orcid.org/0000-0001-7777-0669

Article

Publisher ID: EMMM201911131

DOI: 10.15252/emmm.201911131

PMC ID: 7645378

PubMed ID: 33047515

SO-VID: 899250a4-a475-47d7-8ddc-9b8fe73b7bc0

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date received : 09 July 2019

Date revision received : 20 July 2020

Date accepted : 24 July 2020

Page count

Figures: 5, Tables: 2, Pages: 33, Words: 32282

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source-schema-version-number 2.0

cover-date 06 November 2020

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:06.11.2020

ScienceOpen disciplines: Molecular medicine

Keywords: bone sarcoma,molecular diagnostics,molecular medicine,soft tissue sarcoma,targeted therapy,cancer,molecular biology of disease,musculoskeletal system

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: bone sarcoma, molecular diagnostics, molecular medicine, soft tissue sarcoma, targeted therapy, cancer, molecular biology of disease, musculoskeletal system

Sarcoma treatment in the era of molecular medicine

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Genes & Diseases

Most cited references 451

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Approaches to treat immune hot, altered and cold tumours with combination immunotherapies

3D bioprinting of tissues and organs.

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Contributors

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Author notes

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