Evidence map›Paper›PMID 41931849›Full record

ReviewBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2026

Aptamers in cancer therapy: Why has clinical translation lagged behind preclinical promise?

Thoa T Tran, Vu L Tran, Melissa L Fishel, Ba-Thong Nguyen, Jianjun Zhang, Salvatore Condello, Xiaoling Zhong, Max Schmidt

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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.

Thoa T TranDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: thoatran@iu.edu.
Vu L TranWisconsin Blood Cancer Research Institute, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Melissa L FishelIndiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Dept of Biochemistry, Molecular Biology, and Pharmacology, USA.
Ba-Thong NguyenBioinformatics Core Facility, Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, HI 96822, USA.
Jianjun ZhangDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA.
Salvatore CondelloIndiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Dept of Biochemistry, Molecular Biology, and Pharmacology, USA; Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Xiaoling ZhongDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Max SchmidtDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Dept of Biochemistry, Molecular Biology, and Pharmacology, USA.

Funding

Indiana Clinical and Translational Sciences InstituteUM1TR004402 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI Sharon M Moe, Sarah Elizabeth Wiehe · 2023 to 2026
$21.6M
NCATS NIH HHS UM1 TR004402
6 · The paper itself

Abstract

Aptamers have attracted substantial interest as cancer therapeutics due to their high target specificity, chemical programmability, and versatility in drug and RNA delivery; however, despite extensive preclinical development, clinical translation in oncology has remained extremely limited, with no aptamer-based therapies approved for cancer indications to date. This gap reflects not a failure of binding affinity, but a fundamental misalignment between aptamer selection and evaluation paradigms and the biological complexity of human tumors. Most aptamers are selected against purified proteins or homogeneous cell lines that fail to capture tumor heterogeneity, dynamic target regulation, and microenvironmental influences encountered in patients, while inconsistent assessment of pharmacokinetics, biodistribution, and functional activity further limits translational predictability. Through analysis of representative clinical programs, including the systemic nucleolin-targeting aptamer AS1411, the microenvironment-modulating CXCL12 inhibitor NOX-A12, and the locally administered personalized platform AM003, this review highlights how delivery strategy, target context, and clinical deployment critically shape therapeutic outcomes. Recurrent translational barriers related to systemic exposure, tumor accessibility, regulatory pathways, and competition with established modalities are identified, together with lessons from both failed and emerging programs. Finally, we discuss practical strategies to improve clinical alignment, including human-relevant selection models, localized or combination therapies, and AI-assisted design, positioning aptamers for context-appropriate roles in future precision oncology.

Indexed as

Antineoplastic AgentsAptamers, NucleotideNeoplasmsTranslational Research, BiomedicalAnimalsDrug Evaluation, PreclinicalHumansTumor MicroenvironmentAntineoplastic AgentsAptamers, NucleotideAptamer in cancer therapyAptamer translational barriersCombined treatmentOncology aptamer clinical trialsTargeted therapy

Identifiers

PMID41931849
PMCPMC13274474

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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 OpenQuestion graph.