Molecular targeted therapy for advanced or metastatic soft tissue sarcoma

Abstract

Soft tissue sarcomas are a form of rare and heterogeneous neoplasms with high recurrence rate and mortality. Over the past decades, less progress has been achieved. Surgical management with or without adjuvant/neoadjuvant radiotherapy is still the first-line treatment for localized soft tissue sarcomas, and chemotherapy is the additional option for those with high-risk. However, not all patients with advanced or metastatic soft tissue sarcomas benefit from conventional chemotherapy, targeted therapy takes the most relevant role in the management of those resistant to or failed to conventional chemotherapy. Heterogeneous soft tissue sarcomas vary from biological behavior, genetic mutations, and clinical presentation with a low incidence, indicating the future direction of histotype-based even molecule-based personalized therapy. Furthermore, increasing preclinical studies were carried out to investigate the pathogenesis and potential therapeutic targets of soft tissue sarcomas and increasing new drugs have been developed in recent years, which had started opening new doors for clinical treatment for patients with advanced/metastatic soft tissue sarcomas. Here we sought to summarize the concise characteristics and advance in the targeted therapy for the most common subtypes of soft tissue sarcomas.

Accuracy of core needle biopsy for histologic diagnosis of soft tissue sarcoma

“…For instance, we 49 – 51 and others 52 , 53 explore recurrent sarcoma translocations as targets for “liquid biopsy.” Here, circulating DNA harboring a specific translocation is measured to monitor tumor activity, which has relevance for patient follow-up and assessing the success of multimodal sarcoma therapy. Further developments are expected in the area of targeted molecular therapeutics, which will benefit patients with advanced sarcoma 54 .…”

Chloroquine Combined With Rapamycin Arrests Tumor Growth in a Patient-derived Orthotopic Xenograft (PDOX) Mouse Model of Dedifferentiated Liposarcoma

“…The five-year survival rate of well-differentiated is approximately 90%, whereas that of DDLS is 28% (1,24). Because STS is a rare cancer with a small number of patients, the development of new drugs has lagged behind that for other, more frequent cancer types (25). Although pazopanib, eribulin, and trabectedin have been used to treat STS since 2010 (26)(27)(28), antitumor drugs such as doxorubicin and isophosphamide, developed in the 1970s and 1980s, are still the standard first-line treatment for STS (3-7).…”

Role of vascular endothelial growth factors in pathogenesis of soft tissue sarcomas: literature review

“…Похожая закономерность была установлена и для СМТ. Было показано, что уровень тканевой концентрации VEGF у больных СМТ, перенесших в последующем рецидив и метастазирование, был достоверно выше, чем у больных, не имевших такого исхода заболевания [46,47]. Возможно, развитие рецидива опухоли происходит на фоне дисбаланса ангиогенных медиаторов в ней: за счет высокой экспрессии ангиогенных индукторов по сравнению с низкой экспрессией их ингибиторов [44].…”

“…В настоящее время обоснованы важность и необходимость таргетной противоопухолевой терапии в лечении пациентов с СМТ, резистентных к традиционным методам противоопухолевого лечения [46]. Значительная гетерогенность СМТ, их различия в биологическом поведении, генетических мутациях и клинических проявлениях являются прямым указанием на необходимость разработки персонализированной противоопухолевой терапии с учетом гистотипа и молекулярного паттерна опухоли.…”