Exploring TGF-β Signaling in Cancer Progression: Prospects and Therapeutic Strategies.

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• Cancer remains a major global health challenge due to uncontrolled cell growth and metastasis.
• The Transforming Growth Factor-beta (TGF-β) signaling pathway regulates normal physiological processes but is implicated in cancer.
• TGF-β signaling exhibits context-dependent roles, suppressing tumors early and promoting them later.

Purpose of the Study:

• To review the complex cross-talk of the TGF-β signaling pathway with other major pathways (Wnt, NF-κB, PI3K/Akt, Hedgehog).
• To discuss the dual role of TGF-β in different cancer stages.
• To highlight therapeutic strategies and inhibitors targeting the TGF-β pathway for cancer therapy.

Main Methods:

• Literature review focusing on TGF-β signaling mechanisms, pathway interactions, and therapeutic interventions.
• Analysis of canonical (SMAD-dependent) and non-canonical (SMAD-independent) signaling.
• Examination of various inhibitors including ligand traps, small molecule inhibitors (SMIs), monoclonal antibodies (mAbs), and antisense oligonucleotides.

Main Results:

• TGF-β signaling interacts with Wnt, NF-κB, PI3K/Akt, and Hedgehog pathways, influencing cellular functions.
• TGF-β has a dual role in cancer: tumor suppression in early stages and promotion in advanced stages.
• Numerous therapeutic strategies targeting TGF-β signaling are under investigation in preclinical and clinical trials.

Conclusions:

• The intricate TGF-β signaling network and its cross-talk present significant therapeutic opportunities in oncology.
• Targeting TGF-β signaling, through various inhibitors, offers a promising avenue for cancer treatment.
• Combinational therapies involving TGF-β inhibitors may enhance efficacy and overcome resistance in cancer treatment.