Targeting the transcription cycle and RNA processing in cancer treatment

Area of Science:

• Molecular oncology
• Cancer epigenetics
• RNA biology

Background:

• Genomic and epigenomic alterations in cancer dysregulate the transcriptional program and RNA splicing machinery.
• These dysregulations create cancer-specific dependencies, offering potential therapeutic targets.
• Targeting these vulnerabilities presents an alternative strategy for cancer treatment.

Purpose of the Study:

• To evaluate novel therapeutic strategies targeting transcriptional and RNA splicing vulnerabilities in cancer.
• To explore the potential of transcriptional CDK inhibitors and splicing-modulating compounds in preclinical cancer models.
• To assess the therapeutic promise of combination approaches involving novel inhibitors and existing cancer therapies.

Main Methods:

• Development and evaluation of potent and specific transcriptional CDK inhibitors.
• Assessment of chemical compounds designed to impair RNA splicing.
• Investigation of combination therapies including immune or targeted treatments.
• Preclinical studies in cancer models to determine therapeutic potential.

Main Results:

• Transcriptional CDK inhibitors and splicing-modulating compounds demonstrate therapeutic potential in preclinical cancer models.
• Inhibitors targeting transcriptional CDKs, splicing, or PRMT5 show promising results.
• Several novel therapeutic agents have advanced rapidly into early clinical trials.

Conclusions:

• Dysregulation of transcription and RNA splicing in cancer creates unique vulnerabilities that can be therapeutically exploited.
• Targeted inhibition of transcriptional CDKs, splicing machinery, or PRMT5 represents a promising avenue for cancer treatment.
• The rapid advancement of these agents into clinical trials underscores their therapeutic potential in human cancers.