Evidence mapPaperPMID 42082974Full record

ReviewJournal of experimental & clinical cancer research : CR2026

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Prashant Sharma, Nguyen Phuong Thuy, Israrul H Ansari, Ravi Mani Tripathi, Mrinalini Kala, Mostafa H Elberry, Neelesh Sharma, Sung-Jin Lee

Abstract readReview
In one paragraph

Review in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Prashant SharmaDepartment of Child Health, University of Arizona College of Medicine-Phoenix, ABC1 Building, 425 N 5Th Street, Phoenix, AZ, 85004, USA. psharma1@arizona.edu.
Nguyen Phuong ThuyFaculty of Medical Technology, Hanoi Medical University, Building A7, No.1 Ton That Tung, Hanoi, 100000, Vietnam.
Israrul H AnsariDepartment of Pediatrics, Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, 4136 Wisconsin Institutes for Medical Research I, University of Wisconsin, Madison, WI, 53706, USA.
Ravi Mani TripathiAmity Institute of Nanotechnology, Amity University Uttar Pradesh, Sector 125, Noida, UP, 201303, India.
Mrinalini KalaDepartment Internal Medicine, University of Arizona College of Medicine-Phoenix, 475 N. 5th Street, Phoenix, AZ, 85004, USA.
Mostafa H ElberryDepartment of Child Health, University of Arizona College of Medicine-Phoenix, ABC1 Building, 425 N 5Th Street, Phoenix, AZ, 85004, USA.
Neelesh SharmaDivision of Veterinary Medicine, Faculty of Veterinary Sciences and Animal Husbandry, Sher- E-Kashmir University of Agricultural Sciences and Technology of Jammu, Ranbir Singh Pura, Union Territory of Jammu and Kashmir, 181 102, India.
Sung-Jin LeeDepartment of Applied Animal Science, College of Animal Life Sciences, Kangwon National University, Chuncheon, Republic of Korea. sjlee@kangwon.ac.kr.

Funding

National Research Foundation of Korea, South Korea Project No: 2022R1F1A1075002
6 · The paper itself

Abstract

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that directly interface with epigenetic machinery. These TME-activated pathways recruit DNA methyltransferases, histone-modifying enzymes, and regulate microRNA (miRNA) networks, establishing stable resistant phenotypes including epithelial-mesenchymal transition, cancer stem cells, and metabolic adaptation. Critically, miRNA dysregulation serves as a central integrator, creating bidirectional crosstalk between signaling pathways and epigenetic modifications through self-reinforcing circuits. Unlike previous reviews focusing on isolated resistance mechanisms, we demonstrate how this integrated TME-epigenetic axis creates specific therapeutic vulnerabilities exploitable through rationally designed nanotechnology platforms delivering epigenetic modulators (DNMT inhibitors, HDAC inhibitors, EZH2 inhibitors) and gene therapy tools (CRISPR-Cas9 epigenetic editors, miRNA mimics/antagomirs). We critically evaluate clinical translation challenges, including EPR effect heterogeneity, delivery barriers, and biomarker gaps, providing a balanced perspective on both potential and obstacles. This mechanistic framework guides the development of next-generation combination therapies targeting multiple nodes within the TME-epigenetic-nanotherapy axis.

Indexed as

Drug Resistance, NeoplasmEpigenesis, GeneticGenetic TherapyNanotechnologyNeoplasmsTumor MicroenvironmentAnimalsHumansSignal TransductionChemoresistanceCRISPREpigeneticFDAGene TherapyNanotechnologyRegulatory ChallengesTumor Microenvironment

Identifiers

PMID42082974
PMCPMC13322090

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.