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      Recent Insights into Therapy Resistance in Osteosarcoma

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          Abstract

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          Osteosarcoma is the most common cancer of the bone for children and adolescents. Although chemotherapy regimens have been widely available and effective for many patients for decades, there have been few reliable options available when these standard regimens fail to adequately cure the disease. This suggests internal resistance mechanisms that allow the tumor cells to survive. Here, we review many of the recent studies that have provided new insights into understanding and overcoming chemo- and radioresistance in osteosarcoma.

          Abstract

          Osteosarcoma, the most common bone malignancy of childhood, has been a challenge to treat and cure. Standard chemotherapy regimens work well for many patients, but there remain minimal options for patients with progressive or resistant disease, as clinical trials over recent decades have failed to significantly improve survival. A better understanding of therapy resistance is necessary to improve current treatments and design new strategies for future treatment options. In this review, we discuss known mechanisms and recent scientific advancements regarding osteosarcoma and its patterns of resistance against chemotherapy, radiation, and other newly-introduced therapeutics.

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          Long Noncoding RNA and Cancer: A New Paradigm.

          In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81. ©2017 AACR.
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            Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program.

            Osteosarcoma, which is the most common primary bone tumor, occurs most frequently in adolescents, but there is a second incidence peak among individuals aged > 60 years. Most osteosarcoma epidemiology studies have been embedded in large analyses of all bone tumors or focused on cases occurring in adolescence. Detailed descriptions of osteosarcoma incidence and survival with direct comparisons among patients of all ages and ethnicities are not available. Frequency, incidence, and survival rates for 3482 patients with osteosarcoma from the National Cancer Institute's population-based Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2004 were investigated by age (ages 0-24 years, 25-59 years, and 60 to > or = 85 years), race, sex, pathology subtype, stage, and anatomic site. There were large differences in incidence and survival rates by age. There was a high percentage of osteosarcoma with Paget disease and osteosarcoma as a second or later cancer among the elderly. There was a high percentage of osteosarcoma among patients with Paget disease and osteosarcoma as a second or later cancer among the elderly. Tumor site differences among age groups were noted. Survival rates varied by anatomic site and disease stage and did not improve significantly from 1984 to 2004. This comprehensive, population-based description of osteosarcoma, identified important differences in incidence, survival, pathologic subtype, and anatomic site among age groups, and quantified the impact of osteosarcoma in patients with Paget disease or as a second cancer on incidence and mortality rates. These findings may have implications in understanding osteosarcoma biology and epidemiology. (c) 2009 American Cancer Society
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              The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

              Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                30 December 2020
                January 2021
                : 13
                : 1
                : 83
                Affiliations
                [1 ]Texas Children’s Cancer and Hematology Centers and The Faris D. Virani Ewing Sarcoma Center, Houston, TX 77030, USA; yustein@ 123456bcm.edu
                [2 ]Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
                Author notes
                Author information
                https://orcid.org/0000-0002-3789-1121
                Article
                cancers-13-00083
                10.3390/cancers13010083
                7795058
                33396725
                d66e0e60-7783-4b67-b521-9f901770bd9a
                © 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
                : 08 December 2020
                : 28 December 2020
                Categories
                Review

                osteosarcoma,chemotherapy resistance,radiation resistance,tumor microenvironment,hypoxia,autophagy

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