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

SIMPLE SUMMARY: Soft tissue sarcomas (STSs) are rare malignant conditions with more than 70 subtypes that are difficult to treat, especially in advanced or metastatic states. Recently, next-generation sequencing technologies have provided comprehensive information and developed personalized medicine for treating cancer in general and STSs in particular. Growing knowledge of diverse gene alterations and biomolecular targets in various subtypes of STSs raises hope for novel treatment approaches and heralds a paradigm shift in the treatment of STSs. Activated cyclin-dependent kinases (CDKs) appear to play a critical role in sarcoma development and represent important targets for sarcoma therapy. This review discusses how CDK signaling influences STS development and its implications for STS prediction and targeted treatment. ABSTRACT: Soft tissue sarcomas (STSs) are tumors that are challenging to treat due to their pathologic and molecular heterogeneity and their tumor biology that is not yet fully understood. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong driver of sarcogenesis. CDKs are enzyme forms that play a crucial role in cell-cycle control and transcription. They belong to the protein kinases group and to the serine/threonine kinases subgroup. Recently identified CDK/cyclin complexes and established CDK/cyclin complexes that regulate the cell cycle are involved in the regulation of gene expression through phosphorylation of critical components of transcription and pre-mRNA processing mechanisms. The current and continually growing body of data shows that CDKs play a decisive role in tumor development and are involved in the proliferation and growth of sarcoma cells. Since the abnormal expression or activation of large numbers of CDKs is considered to be characteristic of cancer development and progression, dysregulation of the CDK signaling pathways occurs in many subtypes of STSs. This review discusses how reversal and regulation can be achieved with new therapeutics and summarizes the current evidence from studies regarding CDK modulation for STS treatment.