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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...

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Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies
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PROTAC-based nanoassemblies targeting BRD4 for potentiate FLASH radiosensitization therapy.

Ruiling Xu1, Xiaowen Han1, Yunfei Sun2

  • 1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China.

Materials Today. Bio
|July 12, 2026
PubMed
Summary

This study introduces a novel nanoplatform (APF) to overcome tumor radioresistance in ultrahigh dose-rate radiotherapy (FLASH-RT). APF enhances FLASH-RT efficacy by degrading BRD4, sensitizing tumors and improving outcomes with minimal toxicity.

Keywords:
Bromodomain-containing protein 4NanoparticlesProteolysis-targeting chimeraRadiosensitizerUltra-high dose rate radiotherapy

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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

Area of Science:

  • Oncology
  • Nanomedicine
  • Radiotherapy

Background:

  • Ultrahigh dose-rate radiotherapy (FLASH-RT) offers normal tissue sparing but faces challenges with tumor radioresistance.
  • Targeted protein degradation presents a novel strategy to overcome treatment resistance in cancer therapy.

Purpose of the Study:

  • To develop a redox-responsive nanoplatform (APF) for targeted delivery of a PROTAC (ARV-771) to enhance FLASH-RT efficacy.
  • To investigate the mechanism of APF in sensitizing tumors to FLASH-RT through BRD4 degradation and disruption of DNA repair pathways.

Main Methods:

  • Self-assembly of folate-conjugated PEG2000-ARV-771 into APF nanoparticles.
  • FA-mediated tumor cell targeting and endocytic uptake, followed by glutathione-triggered release of ARV-771.
  • Assessment of APF-assisted FLASH-RT efficacy in vitro and in vivo, including apoptosis, necrosis, ROS generation, and DNA damage analysis.

Main Results:

  • APF nanoparticles successfully delivered ARV-771, leading to proteasomal degradation of BRD4.
  • BRD4 degradation disrupted the BRD4-c-Myc-RAD51AP1 pathway and suppressed DNA repair genes, sensitizing tumors to FLASH-RT.
  • APF@FLASH-RT combination therapy demonstrated significant tumor inhibition with reduced systemic toxicity and enhanced cancer cell killing.

Conclusions:

  • The novel APF nanoplatform effectively overcomes tumor radioresistance by targeting BRD4 degradation.
  • APF enhances FLASH-RT efficacy through ROS generation and DNA damage, offering a promising strategy for improved cancer treatment.
  • This nanomedicine approach holds potential for advancing FLASH radiotherapy in clinical oncology.