A review of soft-tissue sarcomas: translation of biological advances into treatment measures

Abstract

Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease.

Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance

“…RMS tumors are highly aggressive and typically develop from skeletal muscle cells arising in a variety of anatomic sites in the body 2,3 . There is a slightly higher prevalence of this disease in males than in females, and it is often associated with genetic disorders such as Li-Fraumeni familiar cancer syndrome and neurofibromatosis type 1 2 .…”

“…Based on histologic criteria, RMS tumors are subdivided in two main groups, embryonal (ERMS) and alveolar (ARMS). ERMS account for 60% of all RMS, affecting children under the age of 10, especially around the head and neck regions 2,3 . ARMS represent approximately 20% of all RMS, occurring mostly in adolescents, frequently localized in the limbs 3,4 .…”

“…ERMS account for 60% of all RMS, affecting children under the age of 10, especially around the head and neck regions 2,3 . ARMS represent approximately 20% of all RMS, occurring mostly in adolescents, frequently localized in the limbs 3,4 . The current treatment strategies for RMS include chemotherapy, radiation, and surgery 4 .…”

The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research

“…We aimed to test this hypothesis in angiosarcoma, a disease that represents just 1-2% of soft tissue sarcomas, which in turn, comprise less than 1% of adult malignancies 2,3 . The prognosis for AS is poor, with a reported 5-year disease-specific survival of 38% 2 .…”

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

“…erapeutic efficacy of YK-4-279 was proved in in vitro and in vivo models [19]. e YK4-279 analog TK216 is currently being used in a Phase I clinical trial in patients with relapsed or refractory Ewing's sarcoma [20]. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the genesis of several human cancers, in particular, inflammatory myofibroblastic tumor (IMT), which is characterized by ALK-based chromosomal translocations t(2; 19) (p23; p13.1), t(1; 2) (q22-23; p23), t(2; 17) (p23; q23), t(2; 2) (p23; q23), etc.…”