Consuming a diet rich in vitamin A or its analogs may help prevent children and young adults with acute lymphoblastic leukemia (ALL) reduce their risk of developing painful pancreas inflammation during chemotherapy treatment.
Details about this potential dietary solution to prevent a potentially life-threatening adverse event were published in Science Translational Medicine.
For people with ALL, treatment with the enzyme asparaginase helps starve cancer cells by reducing the amount of asparagine circulating in the blood, which the cancer cells need but cannot make themselves. The medication, often used in combination with other chemotherapies, is given via injection into a vein, muscle, or under the skin.
However, an estimated 2% to 10% of asparaginase users develop inflammation of the pancreas in reaction to asparaginase treatment. For a third of these people, the symptoms can be severe.
The researchers developed predictive analytics using over 100 million data points encompassing gene expression data, small-molecule data, and electronic health records to understand more of the mechanisms driving asparaginase-associated pancreatitis (AAP) and identify potential interventions to prevent or mitigate AAP.
First, they analyzed massive amounts of gene expression data to reveal that gene activity associated with asparaginase or pancreatitis might be reversed by retinoids (vitamin A and its analogs). The team found more supporting evidence by “mining” millions of of electronic health records from the TriNetX database and the U.S. Federal Drug Administration Adverse Events Reporting System.
This number crunching and predictive analytics work included use of the AERSMine software developed. The research team also studied data from mice experiments and compared plasma samples from people with ALL who developed pancreatitis and those who did not.
Ultimately, the team established two sets of human “real-world” experiences. They found that only 1.4% of patients treated with asparaginase developed pancreatitis when they were also taking vitamin A in contrast to 3.4% of patients who did not. Concomitant use of vitamin A correlated with a 60% reduction in the risk of AAP. Lower amounts of dietary vitamin A correlated with increased risk and severity of AAP.
“This study demonstrates the potential of mining ‘real-world’ data to identify therapy modifiers for improving patient outcomes. In cases where a primary drug induces toxicity but is critical to therapy, such as asparaginase, therapy modifiers, such as vitamin A and its analogs, may be of immediate relevance to patients on asparaginase and ‘at-risk’ for AAP,” says a co-first author of the study.
Says the author: "Our study highlights the power of heterogeneous data integration and analysis in translational research. By leveraging existing ‘omics and patient-centric data and a systems approach, we were able to identify new insights into the development of AAP and potential interventions to prevent or mitigate this side effect."
In some ways, learnings from this study could be applied immediately to patient care. However, more clinical research is needed to establish how much vitamin A would be needed to protect ALL patients from pancreatitis; and whether a protective level can be achieved by diet or via supplements. In fact, target vitamin levels may need to vary according to individual differences in metabolism.
https://www.science.org/doi/10.1126/scitranslmed.abn2110
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fa-systems-approach_3&filter=22
Role for retinoids in asparaginase-associated pancreatitis
- 736 views
- Added
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Brain's immune cells put the brakes on neurons
Read more
Reference atlas of small noncoding RNAs in mouse tissues
Read more
Gene expression altered by direction of forces acting on cell
Read more
Reducing lignin levels in plants using CRISPR
Read more
Both excitatory and inhibitory systems play a role in memory consol…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar