Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (752 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Agents, Alkylating; Alkylators; Alkylator; Alkylating Agent; Agent, Alkylating.
Where it fits in the MeSH classification
- Broader topics
- Molecular Mechanisms of Pharmacological Action; Noxae
- Narrower topics
- Antineoplastic Agents, Alkylating
Research landscape
PubMed indexes 19,501 records tagged with the MeSH heading “Alkylating Agents” (counts retrieved 2026-10-29). 2,107 of them (10.8%) were published from 2020 onward, and the busiest period so far is through 1999 with 6,167 records.
Reviews account for 2,343 records (12.0%) and meta-analyses for 104. Randomized controlled trials number 575 (2.9%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 6,167 |
| 2000-2009 | 5,592 |
| 2010-2019 | 5,635 |
| 2020 onward | 2,107 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,343 | 12.0% |
| Meta-analyses | 104 | 0.5% |
| Randomized controlled trials | 575 | 2.9% |
Method: PubMed query "Alkylating Agents"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in pharmacology
Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors.
- Closing excerpt
- Instead inherent cancer cell plasticity emerges as a novel relevant target for treatment.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (144 words)
The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors. Here we report that cells expressing CSC-associated cell membrane markers in Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions, instructed by the microenvironment and is predictable by mathematical modeling. Although functional stem cell properties were similar in vitro, accelerated reconstitution of heterogeneity provides a growth advantage in vivo, suggesting that tumorigenic potential is linked to intrinsic plasticity rather than CSC multipotency. The capacity of any given cancer cell to reconstitute tumor heterogeneity cautions against therapies targeting CSC-associated membrane epitopes. Instead inherent cancer cell plasticity emerges as a novel relevant target for treatment.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30992437 · DOI · PMC6467886
Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting.
- Closing excerpt
- This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (198 words)
Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34593813 · DOI · PMC8484581
Lnc-TALC promotes O6-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes, including therapeutic resistance.
- Closing excerpt
- Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes, including therapeutic resistance. However, the mechanisms underlying lncRNA-mediated temozolomide (TMZ) resistance in glioblastoma (GBM) remain largely unknown. To illustrate the role of lncRNA in TMZ resistance, we induce TMZ-resistant GBM cells, perform a lncRNA microarray of the parental and TMZ-resistant cells, and find an unreported lncRNA in GBM, lnc-TALC (temozolomide-associated lncRNA in glioblastoma recurrence), correlated with TMZ resistance via competitively binding miR-20b-3p to facilitate c-Met expression. A phosphorylated AKT/FOXO3 axis regulated lnc-TALC expression in TMZ-resistant GBM cells. Furthermore, lnc-TALC increased MGMT expression by mediating the acetylation of H3K9, H3K27 and H3K36 in MGMT promoter regions through the c-Met/Stat3/p300 axis. In clinical patients, lnc-TALC is required for TMZ resistance and GBM recurrence. Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31053733 · DOI · PMC6499807
Molecular mechanisms underlying cyclophosphamide-induced ovarian injury and protective strategies [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Cyclophosphamide (CP) is an anti-cancer medication that also treats chronic inflammatory illnesses caused by the immune system.
- Closing excerpt
- Finally, investigation into these molecular pathways may pave the way for early ovarian damage relief and for the development of different agent strategies to alleviate CP-mediated POF.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (260 words)
Cyclophosphamide (CP) is an anti-cancer medication that also treats chronic inflammatory illnesses caused by the immune system. Although CP is widely used, it can occasionally have limited therapeutic efficacy due to its significant combined toxicities. Ovarian damage caused by CP is a major problem for patients, and premature ovarian failure (POF) is a serious side effect of CP that commonly affects female patients. Mechanistic investigations have implicated oxidative stress, inflammatory responses, and apoptosis as critical components in the etiology of CP-induced POF, although the exact process by which this ovarian toxicity occurs remains unclear. After CP causes ovarian cells to generate proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB) is activated. The activation of the NLRP3 inflammasome is the subsequent stage. In addition, Nrf2/HO-1 has been identified as an important signaling pathway that mitigates oxidative stress in CP-induced POF due to its anti-inflammatory and antioxidative characteristics. Moreover, several recent studies highlighted the role of α-klotho deficiency in ovarian aging. Quercetin, resveratrol, berberine, curcumin, irbesartan, mirtazapine, sildenafil, atorvastatin, donepezil, cilostazol, moxibustion, LCZ696, buspirone, levomilnacipran, melatonin, diosmin, and azilsartan are some of the agents that may protect against ovarian injury caused by CP, as shown in Graphical abstract. Our goal in writing this study is to provide a concise overview of the possible redox molecular pathways that cause ovarian harm in CP and how to potentially ameliorate them. Finally, investigation into these molecular pathways may pave the way for early ovarian damage relief and for the development of different agent strategies to alleviate CP-mediated POF.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40938363 · DOI · PMC12901320
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches [5]
- Research article The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy [6]
- Research article Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance [7]
- Research article Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma [8]
- Research article Temozolomide for immunomodulation in the treatment of glioblastoma [9]
- Research article Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision [10]
References
- Dirkse A, Golebiewska A, Buder T, Nazarov PV, Muller A, Poovathingal S, et al.. Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment. . 2019. PMID 30992437 · DOI · PMC6467886
- Liu L, Bai X, Martikainen MV, Kårlund A, Roponen M, Xu W, et al.. Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles. . 2021. PMID 34593813 · DOI · PMC8484581
- Wu P, Cai J, Chen Q, Han B, Meng X, Li Y, et al.. Lnc-TALC promotes O6-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p. . 2019. PMID 31053733 · DOI · PMC6499807
- Sharata EE, Bakry T, Atta HG, Mohammed HA, Diab NS, Atef RA, et al.. Molecular mechanisms underlying cyclophosphamide-induced ovarian injury and protective strategies. . 2026. PMID 40938363 · DOI · PMC12901320
- Joerger AC, Fersht AR. The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches. Annu Rev Biochem. 2016. PMID 27145840 · DOI
- Ahlmann M, Hempel G. The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. Cancer Chemother Pharmacol. 2016. PMID 27646791 · DOI
- Tomar MS, Kumar A, Srivastava C, Shrivastava A. Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance. Biochim Biophys Acta Rev Cancer. 2021. PMID 34419533 · DOI
- Jiapaer S, Furuta T, Tanaka S, Kitabayashi T, Nakada M. Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma. Neurol Med Chir (Tokyo). 2018. PMID 30249919 · DOI · PMC6186761
- Karachi A, Dastmalchi F, Mitchell DA, Rahman M. Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro Oncol. 2018. PMID 29733389 · DOI · PMC6231207
- Iqubal A, Iqubal MK, Sharma S, Ansari MA, Najmi AK, Ali SM, et al.. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sci. 2019. PMID 30552952 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.