STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 targets, necessitating novel therapeutic strategies.
• Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed and activated in TNBC, promoting tumor development and progression.
• The absence of specific molecular targets in TNBC highlights the urgent need for innovative treatment and prevention approaches.

Purpose of the Study:

• To review the current understanding of STAT3's role in TNBC initiation, progression, metastasis, and immune evasion.
• To highlight STAT3 as a critical oncogenic driver in TNBC.
• To discuss existing STAT3 targeting strategies and small molecule inhibitors for TNBC therapy.

Main Methods:

• Literature review of clinical trials and preclinical studies on STAT3 in TNBC.
• Analysis of STAT3's downstream gene regulation in TNBC cell survival, proliferation, migration, and angiogenesis.
• Examination of STAT3 small molecule inhibitors and their efficacy in in vitro and in vivo TNBC models.

Main Results:

• STAT3 activation is crucial for TNBC cell survival, proliferation, invasion, angiogenesis, chemoresistance, and immune evasion.
• STAT3 regulates stem cell self-renewal and differentiation, contributing to TNBC aggressiveness.
• Small molecule STAT3 inhibitors demonstrate significant anticancer activity in preclinical TNBC models.

Conclusions:

• STAT3 is a key therapeutic target for triple-negative breast cancer.
• Targeting STAT3 offers a promising avenue for developing novel preventive and therapeutic strategies for TNBC.
• Further research into developing more specific and effective STAT3 inhibitors is warranted for TNBC treatment.