Unraveling molecular aberrations and pioneering therapeutic strategies in osteosarcoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Osteosarcoma is a rare primary bone cancer with complex molecular characteristics.
• Current therapeutic strategies show limited efficacy, evidenced by stagnant five-year survival rates.
• Molecular profiling advancements offer a deeper understanding of osteosarcoma biology.

Purpose of the Study:

• To review the molecular landscape of osteosarcoma, including cancer predisposition syndromes and actionable genomic alterations.
• To explore current and innovative treatment strategies for osteosarcoma.
• To provide a comprehensive understanding for advancing osteosarcoma management.

Main Methods:

• Literature review focusing on osteosarcoma genetics, predisposition syndromes, and therapeutic interventions.
• Analysis of current treatment modalities: surgery, chemotherapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs).
• Exploration of emerging therapies targeting diverse pathways (e.g., PI3K/mTOR, DNA damage repair) and novel approaches like antibody-drug conjugates (ADCs) and various immunotherapies.

Main Results:

• Osteosarcoma exhibits diverse molecular aberrations and is linked to cancer predisposition syndromes.
• Established treatments like surgery and chemotherapy have limitations.
• Innovative treatments including targeted therapies (TKIs), ADCs, and immunotherapies (ICIs, ACT, cancer vaccines) show promise.

Conclusions:

• A comprehensive understanding of osteosarcoma's molecular complexity is crucial for developing effective treatments.
• Targeting diverse pathways and utilizing novel therapeutic modalities like immunotherapy and ADCs are key to improving patient outcomes.
• This review provides guidance for clinical applications to advance osteosarcoma management.