Genomic-guided precision therapy for soft tissue sarcoma

Abstract

Soft tissue sarcoma (STS), although heterogeneous in histopathology presentation, has mostly been treated with chemotherapy agents as one entity. Our understanding of crucial genomic alterations in different STS histologies and the advent of molecular-targeted agents have reshaped the treatment paradigm for advanced STS. Small-molecule inhibitors of c-KIT, plate-derived growth factor receptor alpha, c-MET, BRAF, anaplastic lymphoma kinase, ROS1 and colony-stimulating factor-1 receptor have been successfully validated in clinical studies to yield practice-changing results. Inhibitors of other novel genomic targets including mouse double minute 2 homolog, cyclin-dependent kinase 4/6, mitogen-activated protein kinase and epigenetic regulators are expected to be developed in the near future. Furthermore, with the advancement and accessibility of molecular diagnosis and next-generation sequencing, a genomic-based therapeutic approach should be widely applicable to advanced STS patients. This review will focus on the progress of genomic-guided therapy tailored to each molecular alteration of different STS histologies.

Current treatment and novel insights regarding ROS1‐targeted therapy in malignant tumors

“…Consistently, Wang et al. 30 , 31 also suggested that ROS1 gene amplification or rearrangement mutations occurred more frequently in malignant tumors, such as gastrointestinal stromal tumors, gallbladder cancer, and soft tissue sarcoma. However, the significance and impact of these mutations require further investigation.…”

“…28 Hou et al 29 studied the cBioPortal for Cancer Genomics and next-generation sequencing (NGS) test results of 177 patients with lung adenocarcinoma and found the frequent occurrence of ROS1 gene rearrangements in younger patients (<40 years old; p = 0.035); however, the significance of these mutations was unclear. Consistently, Wang et al 30,31 also suggested that ROS1 gene amplification or rearrangement mutations occurred more frequently in malignant tumors, such as gastrointestinal stromal tumors, gallbladder cancer, and soft tissue sarcoma. However, the significance and impact of these mutations require further investigation.…”

Organoids: opportunities and challenges of cancer therapy

“…With the development of biomedicine, it was found that drug response of tumor patients varied even though drugs were treated at the same dose, especially for some target-specific antitumor drugs ( Ward et al, 2021 ). Further studies revealed that there are various mutations in the tumor tissues of different tumor patients, which might be the reason why anti-tumor targeted drugs did not work well for partial patients ( Chen and Chen, 2020 ). The precision therapy of tumors is an effective response to the current clinical treatment of tumors.…”

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

“…In the United States, there are 12,750 new cases diagnosed yearly, and STSs kill 5270 people each year [ 1 ]. The crude incidence rate of STSs is 4.71 per 100,000 people in Europe, with an estimated 25,851 new cases in the European Union [ 2 ]. Soft tissue sarcoma is currently composed of approximately 80 subtypes defined by the World Health Organization (WHO), classified based on a combination of unique morphological, immunohistochemical, and molecular characteristics [ 3 ].…”