New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Cancer therapies often fail due to drug resistance.
• Tumor cell plasticity, the ability to reversibly change cell identity, is a key mechanism driving cancer progression and drug resistance.
• Transcription factors, particularly from the KLF and SOX families, are implicated in regulating this plasticity.

Purpose of the Study:

• To review recent findings on the roles of KLF4, KLF5, and SOX factors in cancer development and evolution.
• To focus on their involvement in cancer initiation, invasion, tumor hierarchy, heterogeneity, and lineage plasticity.
• To discuss novel therapeutic strategies targeting these transcription factors for cancer treatment.

Main Methods:

• Literature review of recent studies on KLF and SOX family transcription factors in cancer.
• Analysis of their roles in various aspects of cancer pathogenesis and plasticity.
• Exploration of emerging drug development approaches like PROTAC and protein-protein interaction (PPI) targeting.

Main Results:

• KLF4, KLF5, and SOX factors play critical roles in regulating tumor cell plasticity, contributing to cancer stemness and drug resistance.
• These transcription factors are involved in fundamental cancer processes including initiation, invasion, and the establishment of tumor hierarchy and heterogeneity.
• Targeting these transcription factors presents a promising avenue for developing novel cancer therapies.

Conclusions:

• Understanding the regulation of tumor cell plasticity by KLF and SOX factors is crucial for overcoming cancer drug resistance.
• Emerging technologies offer potential ways to target previously "undruggable" transcription factors.
• Targeted therapies focused on transcriptional regulation hold promise for improving cancer treatment outcomes.