Evidence map›Paper›PMID 42320877›Full record

ArticleCancer letters2026

Orthogonally targeted tumor radiosensitization using cell penetrating peptide-ATM inhibitor conjugates to stimulate anti-tumor immune responses.

Kanika Dhawan, Michael M Allevato, Jacqueline Lesperance, Maria F Camargo, Marcus M Cheng, Mahsa Mortaja, Bamdad Zareh, Dina V Hingorani, Stephen R Adams, J Silvio Gutkind and 1 more

Abstract read
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In one paragraph

Article in Cancer letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Kanika DhawanDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA; UC San Diego, Moores Cancer Center, La Jolla, CA, 92093, USA. Electronic address: kdhawan@health.ucsd.edu.
Michael M AllevatoDepartment of Pharmacology, University of California San Diego, La Jolla, CA, 92093, USA.
Jacqueline LesperanceDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Maria F CamargoDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Marcus M ChengDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Mahsa MortajaDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Bamdad ZarehDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Dina V HingoraniDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Stephen R AdamsDepartment of Pharmacology, University of California San Diego, La Jolla, CA, 92093, USA.
J Silvio GutkindDepartment of Pharmacology, University of California San Diego, La Jolla, CA, 92093, USA; UC San Diego, Moores Cancer Center, La Jolla, CA, 92093, USA.
Sunil J AdvaniDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA; UC San Diego, Moores Cancer Center, La Jolla, CA, 92093, USA. Electronic address: sjadvani@health.ucsd.edu.

Funding

Elucidation and therapeutic exploitation of PAK mediated radioresistanceR37CA215081 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADVANI, SUNIL J · 2018 to 2024
$2.5M
Spatially precise radio-chemo-immunotherapy using antibody conjugatesR01CA268513 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sunil J Advani · 2023 to 2026
$2.1M
NCI NIH HHS R01 CA268513NCI NIH HHS R37 CA215081
6 · The paper itself

Abstract

Tumor resistance to radiotherapy continues to be a significant problem in improving cancer patient outcomes. To overcome radioresistance, drugs that sensitize cancer cells to ionizing radiation (IR) have been tested. In theory, radiosensitizers should increase irradiated tumor kill and improve patient outcomes. However, in practice, the clinical utility of such drugs is curtailed by radiosensitization of peri-tumoral normal tissues causing toxicities. To target radiosensitizer delivery to tumors, we developed an activatable cell penetrating peptide (ACPP) drug conjugate for spatially tumor-restricted delivery of the potent ataxia-telangiectasia mutated kinase inhibitor (ATMi) AZD0156. The ACPP scaffold cloaks a cell penetrating peptide-drug conjugate until it is unmasked within tumors through tumor-associated matrix metalloproteinase thus promoting preferential tumor uptake. Using clinically validated antibody-drug conjugate linker chemistry, we conjugated AZD0156 to ACPP (ACPP-AZD0156) and evaluated its immune stimulating and therapeutic activity with IR in immune-competent murine cancer models. Transcriptomic profiling revealed combining ACPP-AZD0156 with IR enhanced radiation-induced immune activation programs, including type I interferon signaling and leukocyte activation network. Importantly, ACPP-AZD0156 combined with IR stimulated intratumoral CD8

Indexed as

Ataxia Telangiectasia Mutated ProteinsCell-Penetrating PeptidesNeoplasmsProtein Kinase InhibitorsRadiation-Sensitizing AgentsAnimalsCell Line, TumorFemaleHumansMiceAtaxia Telangiectasia Mutated ProteinsCell-Penetrating PeptidesProtein Kinase InhibitorsRadiation-Sensitizing AgentsCell penetrating peptide-drug conjugateImmunotherapyRadiosensitizerRadiotherapy

Identifiers

PMID42320877

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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.