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      Precision Medicine in Soft Tissue Sarcoma Treatment

      review-article
      * ,
      Cancers
      MDPI
      soft tissue sarcoma, molecular targeted therapy, precision medicine, whole genome sequencing

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          Abstract

          Soft tissue sarcoma (STS) is a rare component of malignant diseases. STS includes various histological subtypes, and there are some important differences among the different histological subtypes regarding the mutation profile and sensitivity to antitumor agents. Many clinical trials of STS incorporating many different histological subtypes in various populations have been conducted; it is difficult to compare the findings and make conclusions about clinical efficacy. Targeted therapies focusing on specific histological subtypes and precision therapy focusing on the specific genetic mutation(s) of each STS patient are being investigated. Since STS patients are a small population, new clinical trial designs are required to evaluate and establish new targeted therapies for each histological subtype that has a limited number of patients, and preclinical investigations are needed to detect targetable mutations. Now that cancer genome profiling is used in clinical practice, it is urgently necessary to connect the genome profiling data obtained in clinical settings to the optimal clinical treatment strategies. Herein we review the development and challenges of precision therapy in the management of STS patients.

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          Most cited references82

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          Mechanisms and regulation of endothelial VEGF receptor signalling.

          Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are uniquely required to balance the formation of new blood vessels with the maintenance and remodelling of existing ones, during development and in adult tissues. Recent advances have greatly expanded our understanding of the tight and multi-level regulation of VEGFR2 signalling, which is the primary focus of this Review. Important insights have been gained into the regulatory roles of VEGFR-interacting proteins (such as neuropilins, proteoglycans, integrins and protein tyrosine phosphatases); the dynamics of VEGFR2 endocytosis, trafficking and signalling; and the crosstalk between VEGF-induced signalling and other endothelial signalling cascades. A clear understanding of this multifaceted signalling web is key to successful therapeutic suppression or stimulation of vascular growth.
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            Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial.

            Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.
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              Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial.

              Molecularly targeted agents have been reported to have anti-tumour activity for patients whose tumours harbour the matching molecular alteration. These results have led to increased off-label use of molecularly targeted agents on the basis of identified molecular alterations. We assessed the efficacy of several molecularly targeted agents marketed in France, which were chosen on the basis of tumour molecular profiling but used outside their indications, in patients with advanced cancer for whom standard-of-care therapy had failed.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                16 January 2020
                January 2020
                : 12
                : 1
                : 221
                Affiliations
                Department of Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; s.takahashi-chemotherapy@ 123456jfcr.or.jp
                Author notes
                [* ]Correspondence: kenji.nakano@ 123456jfcr.or.jp ; Tel.: +81-3-3520-0111
                Author information
                https://orcid.org/0000-0002-3721-004X
                Article
                cancers-12-00221
                10.3390/cancers12010221
                7017346
                31963219
                222489b0-b2a4-4137-948a-4bb169b1a178
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 December 2019
                : 15 January 2020
                Categories
                Review

                soft tissue sarcoma,molecular targeted therapy,precision medicine,whole genome sequencing

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