Current Approaches for Personalized Therapy of Soft Tissue Sarcomas.

Kirill I Kirsanov,Beniamin Yu Bokhyan,Timur I Fetisov,Marianna G Yakubovskaya,Gennady A Belitsky,Ekaterina A Lesovaya

doi:10.1155/2020/6716742

Kirill I Kirsanov, Beniamin Yu Bokhyan + Show 4 more

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https://doi.org/10.1155/2020/6716742

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Journal: Sarcoma	Publication Date: Mar 31, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: Russian Cancer Research Center NN Blokhin

Abstract

Soft tissue sarcomas (STS) are a highly heterogeneous group of cancers of mesenchymal origin with diverse morphologies and clinical behaviors. While surgical resection is the standard treatment for primary STS, advanced and metastatic STS patients are not eligible for surgery. Systemic treatments, including standard chemotherapy and newer chemical agents, still play the most relevant role in the management of the disease. Discovery of specific genetic alterations in distinct STS subtypes allowed better understanding of mechanisms driving their pathogenesis and treatment optimization. This review focuses on the available targeted drugs or drug combinations based on genetic aberration involved in STS development including chromosomal translocations, oncogenic mutations, gene amplifications, and their perspectives in STS treatment. Furthermore, in this review, we discuss the possible use of chemotherapy sensitivity and resistance assays (CSRA) for the adjustment of treatment for individual patients. In summary, current trends in personalized management of advanced and metastatic STS are based on combination of both genetic testing and CSRA.

Highlights

Soft tissue sarcomas (STS) present a highly heterogeneous cancer group with more than 50 subtypes in terms of anatomical location, histology, molecular characteristics, and prognosis [1]
Surgery is the standard of care for primary soft tissue sarcomas, while for locally advanced or metastatic STS, chemotherapy is generally the principal treatment modality [3]
Efficacy of tyrosine kinase inhibitors imatinib and sunitinib was approved for COL1A1-PDGFB-positive dermatofibrosarcoma treatment or involved in clinical trials of Phase I-III ([5,6,7] and Table 1). e first part of this review will summarize the approaches of targeted STS therapy based on genetic alteration associated with distinct tumor types

Summary

Introduction

Soft tissue sarcomas (STS) present a highly heterogeneous cancer group with more than 50 subtypes in terms of anatomical location, histology, molecular characteristics, and prognosis [1]. Us, the development of low molecular weight inhibitors of chimeric kinase ETV6-NTRK3, specific for congenital fibrosarcoma/mesoblastic nephroma, is at the Phase I clinical trial ([4] and Table 1). Efficacy of tyrosine kinase inhibitors imatinib and sunitinib was approved for COL1A1-PDGFB-positive dermatofibrosarcoma treatment or involved in clinical trials of Phase I-III ([5,6,7] and Table 1). Phenotypic or functional screening can be an alternative to overcome this gap It refers to the identification of antisarcoma activity of individual drugs or drug combinations using cell- or tissue-based models: chemosensitivity and resistance assays (CSRA). E development of CSRA was started in 1970s for identification of anticancer drugs for individual patients, and the first assays were based on colony-forming efficiency of tumor-derived cells in the presence of various drugs [8, 9]. In the second part of the review, we will discuss possible use of CSRA for the optimization of sarcoma treatment and current progress in the field

Molecular Targeting Therapies for STS

Findings

Conclusion