Related Experiment Video
Updated: Jun 30, 2025
06:21
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
690
Risk factors associated with high-dose methotrexate induced toxicities
Wenshu Li1,2, Jiayi Mo1,2, Zhilin Yang1,2
1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China.
Expert Opinion on Drug Metabolism & Toxicology
|March 19, 2024
Summary
Identifying early risk factors for high-dose methotrexate (HDMTX) toxicity is crucial for personalized cancer treatment. This review synthesizes factors like drug interactions and genetic variations to improve patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- High-dose methotrexate (HDMTX) therapy is vital for neoplasms but presents challenges due to variable pharmacokinetics and adverse effects.
- Individualized patient factors significantly influence HDMTX efficacy and toxicity.
- Early identification of toxicity risks is essential for optimizing treatment strategies.
Purpose of the Study:
- To identify early risk factors for high-dose methotrexate (HDMTX)-induced toxicities.
- To facilitate personalized treatment approaches for patients undergoing HDMTX therapy.
- To improve therapeutic outcomes in neoplasms treated with HDMTX.
Main Methods:
- A systematic review of PubMed and Cochrane databases was performed.
- Inclusion criteria encompassed reviews, clinical trials, and real-world analyses.
- Manual searches and citation reviews supplemented database searches.
Main Results:
- Identified risk factors include MTX exposure, drug interactions, and patient demographics.
- Biochemical factors like serum albumin, urine pH, and serum calcium are significant.
- Genetic polymorphisms (e.g., SLCO1B1, MTHFR, ARID5B, UGT1A1, PNPLA3) and epigenetics play a role in MTX toxicity.
Conclusions:
- This review provides a comprehensive understanding of HDMTX toxicity risk factors.
- Early identification of these factors aids researchers and clinicians in managing HDMTX therapy.
- Personalized treatment strategies based on identified risks can optimize therapeutic outcomes for hematologic malignancies.
Related Concept Videos
01:29Pulmonary Tuberculosis I
242
Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
242
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
163
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
163
01:26Toxic Reactions: Overview
972
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
972
02:56Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
01:46Electron Transport Chain: Complex I and II
13.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.2K
01:17Phase II Reactions: Methylation Reactions
186
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
186