Microbial L-asparaginase as a promising enzyme for treatment of various cancers
Farshad Darvishi1,2, Zohreh Jahanafrooz3, Ahad Mokhtarzadeh4
1Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran. f.darvishi@alzahra.ac.ir.
Abstract:
Metabolic differences between normal and cancerous cells have been used as a point of view for developing anticancer drugs. Some degrading enzymes of certain amino acids have been regarded to kill cancerous cells. L-Asparaginase (ASNase) has shown an excellent therapeutic response to asparagine-auxotrophic cancers such as acute lymphoblastic leukemia (ALL). Some bacteria, yeasts, molds, plants, and animals produce ASNase. Bacterial ASNases from Escherichia coli and Erwinia chrysanthemi are the FDA-approved drugs for ALL treatment. Here, we review new natural prokaryotic and eukaryotic sources of ASNases, recent advances to introduce improvement strategies for the production of recombinant ASNases as well as their chemical modifications, immobilization, nanoencapsulation, and in silico studies to increase efficiency and decrease side effects. Recent studies for application of ASNases to treatment of asparagine-auxotrophic cancers, especially solid cancers, have been reviewed. Furthermore, challenges and future perspectives are discussed for this promising therapeutic enzyme. KEY POINTS: • Review recent advances to introduce new sources of microbial L-asparaginases. • Review improvement strategies for the development of stable and non-toxic L-asparaginases. • Review microbial L-asparaginase application in various cancers' treatment.
Insights
L-Asparaginase (ASNase) enzymes target metabolic differences in cancer cells, offering a promising treatment for asparagine-dependent leukemias. Research explores new sources and modifications to enhance ASNase efficacy and reduce side effects in various cancers.
Area of Science:
- Biochemistry
- Enzymology
- Cancer Therapeutics
Background:
- Metabolic discrepancies between normal and cancerous cells are key targets for anticancer drug development.
- Amino acid-degrading enzymes, like L-Asparaginase (ASNase), demonstrate efficacy against specific cancer types.
- Bacterial ASNases from E. coli and E. chrysanthemi are FDA-approved for treating acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To review novel prokaryotic and eukaryotic sources of ASNases.
- To explore strategies for improving recombinant ASNase production and therapeutic properties.
- To discuss the application of ASNases in treating asparagine-auxotrophic cancers, including solid tumors.
Main Methods:
- Literature review of recent advancements in ASNase research.
- Analysis of strategies for chemical modification, immobilization, and nanoencapsulation of ASNases.
- Inclusion of in silico studies for optimizing enzyme efficiency and minimizing adverse effects.
Main Results:
- Identification of new natural sources for ASNase production.
- Advancements in recombinant ASNase engineering for enhanced stability and reduced toxicity.
- Emerging applications of ASNases beyond leukemia, particularly in solid cancers.
Conclusions:
- ASNase remains a potent therapeutic agent for asparagine-auxotrophic cancers.
- Ongoing research focuses on optimizing ASNase through various biotechnological approaches.
- Future directions include overcoming challenges to broaden ASNase applications and improve patient outcomes.
More Related Videos
08:01Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology
Published on: March 22, 2012
08:35Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
Published on: January 4, 2012
Related Concept Videos
Targeted Cancer Therapies
There are several types of targeted therapies against...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
