THE LANCET

Healthy lifestyle associated with reduced mortality risk in childhood cancer survivors

• Despite huge improvements in five-year survival, adult survivors of pediatric cancer have four times the risk of death as the general population.

• Based on data from the Childhood Cancer Survivor Study (CCSS), St. Jude researchers found that a healthy lifestyle was associated a significantly reduced risk of death in survivors.

• Promoting healthy behaviors including effective prevention and control of cardiovascular disease risk factors demonstrated improvement in survivor’s health space and lifespan.

Nature

Humans vs. bacteria: differences in ribosome decoding revealed

• Ribosomes are molecular machines within cells responsible for synthesizing proteins by decoding messenger RNA (mRNA). Change in mRNA decoding accuracy have been linked to aging and disease.

• Comprehensive studies of human ribosomes are necessary to identify new treatments for cancer and viral infections.

• St. Jude scientists used state-of-the-art structural biology tools and techniques to examine the human ribosome decoding mechanism. They uncovered key differences between bacterial and human ribosomes that reveal new potential therapeutic targets.

Nature

SWI/SNF complexes “bookmark” cell identity during division

• The SWI/SNF complex is one of several factors that control chromatin architecture to regulate gene expression. Abnormalities in the SWI/SNF complex are found in approximately 20% of all cancers, and in several types of neurodevelopmental disorders.

• Using pediatric rhabdoid tumors as a model, St. Jude scientists have uncovered a previously unappreciated role for SWI/SNF complex subunits in mitotic regulation. When a cell divides, it retains information, or ‘memory’, about how to grow and what time of cell to become.

• Researchers discovered how subunits of SWI/SNF act as “bookmarks” during cell division to safeguard cell identity. Loss of SWI/SNF complex subunits in pediatric cancers may be a key component that enables cells to stay in a cancerous state.

Nature

Epigenetic landscape modulates pioneer transcription factor binding

• DNA is tightly wound around proteins called histones and packaged into structures called nucleosomes. Changes in the structure of these elements are implicated in many cancers.

• St. Jude scientists explored how certain proteins in a cell access tightly wound DNA to alter the expression of genes. The work reveals how changes in the genetic blueprint, beyond the discrete sequence of DNA (‘epigenetics’), can influence protein interactions in a cell.

• Understanding the basic mechanisms of how proteins control the expression of genes may reveal potential therapeutic avenues for pediatric cancer and other diseases.

CELL Capturing transporter structure paves the way for drug development

• Substances are escorted across cellular membranes by transporters. One of these substances, sphingosine-1-phosphate (S1P), regulates the immune system, mediates blood vessel formation, and aids in the progression and survival of cancer cells.

• Using sophisticated microscopy approaches, St. Jude scientists revealed the structure of the transporter that mediates S1P function.

• The researchers identified a small molecule inhibitor that blocks the function of the S1P transporter, revealing new avenues for therapeutic development.

CELL St. Jude finds NLRP12 as a new drug target for infection, inflammation and hemolytic diseases

• Many diseases including malaria, SARS-CoV-2 virus infection, or sickle cell disease cause red blood cells to rupture (‘hemolysis’) and release hemoglobin, the oxygen-binding molecule.

• Heme, or degraded hemoglobin, in the bloodstream is associated with increased inflammation and multi-organ failure. St. Jude scientists discovered the key detector of heme that turns on this inflammatory cell death.

• This work was the first to identify a potential druggable target to reduce inflammation caused by infection and hemolytic diseases.

LANCET ONCOLOGY Clinical trial improves neurocognitive outcomes for childhood craniopharyngioma

• Craniopharyngioma is a rare pediatric brain tumor typically treated with traditional radiation therapy. Despite improved survival rates, patients experiencing a high risk of neurological deficits.

• A St. Jude Phase 2 clinical trial treat patients with proton therapy, an alternative to conventional radiotherapy that decreases the amount of normal brain tissue exposed to radiation.

• Patients treated with proton therapy achieved similar survival with fewer cognitive side effects. This work suggests that proton therapy should be the new ‘gold standard’ treatment for craniopharyngioma.

Nature Biomedical Engineering

Prime editing shows proof of concept for treating sickle cell disease

• Sickle cell disease is a serious blood disorder affecting millions of people and caused by a mutation in a subunit of the gene encoding the oxygen-carrying molecule, hemoglobin.

• St. Jude researchers used a groundbreaking gene editing approach, ‘prime editing’, to correct the mutation in blood stem cells from SCD patients. When these cells were transplanted into a preclinical model of SCD, 45% of circulating red blood cells had the healthy form of hemoglobin.

• The work provides proof of concept for how genome ‘prime editing’ might be more effective than conventional genetic editing and could lead to cures for genetic anemias.

Nature Communications

St. Jude targets cancer-causing fusions’ weak spot

• For decades, scientists have observed mutations that combine two genes, resulting in the creation of a hybrid protein that drives cancer (fusion oncogenes).

• Many cancers depend on these fusion proteins to survive and targeting them with drugs is challenging because each individual protein is critical in healthy cells.

• Scientists at St. Jude have developed a computational tool, much like a periodic table for types of oncogenic fusions, that reveals more detail about the genetic sequence of fusion proteins.

• Researchers provided proof-of-principle that highly specific genome editing, using the CRISPR-Cas9 system and data from their computational tool, can inhibit cancer growth in cellular models.

Nature Communications

St. Jude tool gets more out of multi-omics data

• Many cancers have ‘hidden’ drivers that could be targeted therapeutically if they could be identified.

• St. Jude scientists have uncovered, within multi-omics datasets, difficult-to-identify proteins that drive biological processes contributing to cancer.

• Using advanced computational tools and technologies, the researchers found ‘hidden’ drivers, many that are targets of FDA approved drugs. These findings could facilitate faster movement into clinical trials or become the basis of novel drug development.