Transcription therapy

At St. Jude, transcription therapy is used to treat certain pediatric cancers. Recent advances by our researchers and clinicians are harnessing the promise this emerging field offers for targeted treatments.

What is transcription therapy?

Transcription therapy is founded on understanding the causes of aberrant gene expression and designing molecules to counteract and rectify those abnormal processes for therapeutic benefits. Transcription therapy offers the potential to remedy malfunctioning gene “circuits” that cause cancer and other diseases.

Transcription therapy advances

At St. Jude, we have spent decades researching pediatric cancers and catastrophic diseases. This work led us to a growing understanding of the molecular and genetic mechanisms that underlie these diseases. We now know that anomalous epigenetic changes, disruption in chromatin states and errors in transcriptional regulation can lead to certain pediatric cancers and other catastrophic diseases.

Researchers at St. Jude have had enormous success targeting transcription factors, notably by applying glucocorticoid receptor agonists for pediatric patients with acute lymphoblastic lymphoma (ALL). This has resulted in a 94% survival rate for all of our newly diagnosed ALL patients.  Glucocorticoid receptors (GR), as well as several other members of the nuclear receptor class of gene regulatory transcription factors, are targets of nearly 16% of all FDA-approved drugs.

Targeting “undruggable” genes

Despite successes in targeting nuclear receptors for diseases such as cancer, asthma and neurological disorders, transcription factors outside of the nuclear receptor family have been considered difficult to target and are often deemed undruggable. 

While the profound importance of controlling aberrant gene transcription is widely recognized, targeting how genomes are read and deciphered has not been very successful. However, more recent advances in our understanding and ability to design chemical and biological therapeutics are showing great promise. Recent advances offer the potential for a greater ability to target gene transcription and provide novel therapies for a wide range of diseases, including pediatric leukemias, gliomas, brain cancers, and neurological and immune disorders.

Driving progress in transcription therapy research

At St. Jude, a large and diverse group of researchers and clinicians is driving efforts to target gene regulation and grow our understanding of the mechanisms behind pediatric cancer and other diseases. 

From chemists looking at drugs and making molecules to clinicians treating children every day, research into transcription therapeutics includes a wide range of departments and divisions across the institution and our Comprehensive Cancer Center. Working together allows us to examine how mechanistic insight can be tied to clinical outcomes and how clinical indications connect back to our understanding of the disease.  

Transcription Therapy Symposium

Our work and commitment is not limited to the walls of St. Jude. We also have crucial collaborations with leading scientific and clinical institutions around the world. One of our key objectives in these collaborations is to engage the global scientific community and envision new solutions to remedy disease-causing malfunctions in gene transcription. To enable this collaborative engagement, we began hosting the Transcription Therapy Symposium in 2020.

As part of the Bringing Chemistry to Medicine Symposium, the Transcription Therapy Symposium brings together leaders in chemical and biomedical sciences to learn and share advances in transcription therapies for a range of diseases. The event is hosted by the St. Jude Department of Chemical Biology and Therapeutics and the Comprehensive Cancer Center. and will be next held October 2-3, 2025.

Symposium topics included chromatin, transcription factors and emerging concepts in the field. Presenters explored a variety of developments, including:

• The role chromatin remodelers in cancer
• Synthetic gene regulators for neurodegenerative diseases
• Phase separation and drugs targeting transcriptional condensates
• Chemical approaches to modulate epigenetic marks and chromatin landscapes
• Rationally engineered degraders of cyclin dependent kinases (CDKs) that control transcription