Clinical development of therapies targeting TGFβ: current knowledge and future perspectives

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Transforming growth factor beta (TGFβ) is a cytokine with dual roles in cancer, acting as a tumor suppressor in early stages and an oncogene in advanced tumors.
• In advanced cancers, TGFβ promotes tumor progression by creating an immunosuppressive microenvironment and driving proliferation, invasion, and metastasis.

Purpose of the Study:

• To review the status and conclusions of clinical trials investigating TGFβ pathway inhibitors for cancer therapy.
• To discuss challenges in clinical development and explore future directions, including combination therapies and biomarker discovery.

Main Methods:

• Comprehensive review of completed and ongoing clinical trials of TGFβ inhibitors.
• Analysis of preclinical data and clinical trial outcomes.
• Discussion of emerging strategies like combination therapy and biomarker identification.

Main Results:

• Over 15 years of clinical trials have yielded limited success, with no TGFβ inhibitors currently approved for cancer therapy.
• Clinical development is shifting towards combination therapies, particularly with immune checkpoint inhibitors.
• Biomarker research is crucial for identifying patient populations likely to benefit from TGFβ blockade.

Conclusions:

• Targeting the TGFβ pathway remains a promising strategy for cancer treatment, but clinical translation has been slow.
• Future success hinges on innovative trial designs, combination therapies, and robust biomarker strategies.
• Further research is essential to overcome development challenges and realize the therapeutic potential of TGFβ inhibitors.