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Published on: April 22, 2019
STAT3 and Its Targeting Inhibitors in Oral Squamous Cell Carcinoma
Mingjing Jiang1,2, Bo Li1,2
1Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Department of Oral Anatomy and Physiology, Hospital of Stomatology, Jilin University, Changchun 130021, China.
Abstract:
Oral squamous cell carcinoma (OSCC) usually originates from the precancerous lesions of oral mucosa and accounts for approximately 90% of oral cancers. Current therapeutic approaches do not yet meet the needs of patients, and the 5-year survival rate of patients with OSCC is only 50%. Recent studies have revealed that the signal transducer and activator of transcription 3 (STAT3) plays a key role in the development and progression of OSCC. STAT3 is overexpressed and constitutively activated in OSCC cells, and promotes cancer cell proliferation and anti-apoptosis, migration and invasion, angiogenesis, radiotherapy resistance, and immune escape, as well as stem cell self-renewal and differentiation by regulating the transcription of its downstream target genes. Inhibitors of the STAT3 signaling pathway have shown the promising anticancer effects in vitro and in vivo, and STAT3 is expected to be a molecular target for the treatment of OSCC. In this review, we highlight the oncogenic significance of STAT3 in OSCC with an emphasis on the therapeutic approaches and effective small molecule inhibitors targeting STAT3. Finally, we also propose the potential research directions in the expectation of developing more specific STAT3 inhibitors for OSCC treatment.
Insights
Signal transducer and activator of transcription 3 (STAT3) drives oral squamous cell carcinoma (OSCC) progression. Targeting STAT3 with small molecule inhibitors shows promise for developing new OSCC treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cancers, with a poor 5-year survival rate of 50%.
- Current OSCC therapies are insufficient, necessitating novel therapeutic strategies.
- The signal transducer and activator of transcription 3 (STAT3) pathway is implicated in OSCC development and progression.
Purpose of the Study:
- To review the oncogenic role of STAT3 in oral squamous cell carcinoma.
- To emphasize therapeutic strategies and small molecule inhibitors targeting STAT3.
- To propose future research directions for developing specific STAT3 inhibitors for OSCC.
Main Methods:
- Literature review focusing on the role of STAT3 in OSCC.
- Analysis of STAT3's downstream target genes and their functions in cancer.
- Evaluation of existing and potential STAT3 inhibitors for OSCC treatment.
Main Results:
- STAT3 is overexpressed and constitutively active in OSCC, promoting proliferation, anti-apoptosis, migration, invasion, angiogenesis, and immune escape.
- STAT3 regulates cancer stem cell self-renewal and differentiation.
- STAT3 signaling pathway inhibitors demonstrate significant anticancer effects in preclinical studies.
Conclusions:
- STAT3 is a critical oncogenic driver in OSCC.
- Targeting STAT3 represents a promising therapeutic strategy for OSCC.
- Further development of specific STAT3 inhibitors is crucial for advancing OSCC treatment.
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