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Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
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...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...

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A Novel DRD2 Antagonist, SD2-2305, Exerts Anticancer Effects in Colorectal Cancer Cells through G1 Arrest and Caspase-Dependent Apoptosis.

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Updated: Jul 15, 2026

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes
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Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes

Published on: August 24, 2021

Exploiting Macropinocytosis Drives Redox Vulnerability to Preferentially Target Drug-Resistant Cancer.

Jin Hong Lim1, Yuna Kim2, Seok-Mo Kim1

  • 1Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 06273, Republic of Korea.

ACS Nano
|July 14, 2026
PubMed
Summary

Therapy-resistant cancers exploit enhanced macropinocytosis for survival. A novel polymer-metal complex, PPS02, targets this pathway, inducing cancer cell death while sparing normal cells.

Keywords:
colorectal cancerferrous ironhydrogen peroxidepatient-derived metastatic cellspolyaspartic acid sodium salt−metal complexreactive oxygen speciesselenomethionine

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Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy
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Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes
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Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy
07:31

Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy

Published on: August 19, 2021

Area of Science:

  • Oncology
  • Materials Science
  • Biochemistry

Background:

  • Therapy-resistant cancers often exhibit metabolic adaptations, such as enhanced macropinocytosis, to survive stress.
  • Macropinocytosis allows cancer cells to scavenge nutrients and maintain redox balance, contributing to treatment resistance.

Purpose of the Study:

  • To develop a novel polymer-metal strategy targeting cancer cell macropinocytosis.
  • To investigate the potential of this strategy in overcoming therapy resistance and reducing systemic toxicity.

Main Methods:

  • Development of PPS02, a polyaspartic acid sodium salt-based metal complex.
  • Assessment of PPS02's preferential uptake by cancer cells via macropinocytosis.
  • Evaluation of PPS02-induced intracellular H2O2 accumulation, ROS overload, and necroptotic cell death.
  • Testing in patient-derived metastatic colorectal cancer cells and xenograft models.

Main Results:

  • PPS02 demonstrated cancer-preferential uptake, with significantly elevated macropinocytic activity in metastatic colorectal cancer cells compared to normal cells.
  • PPS02 induced necroptotic cell death in both nonmetastatic and platinum-resistant colorectal cancer cells with negligible cytotoxicity to normal cells.
  • In vivo studies showed PPS02 induced sustained tumor regression in patient-derived xenografts without significant systemic toxicity, unlike cisplatin.

Conclusions:

  • Macropinocytosis-driven redox imbalance is a therapeutically exploitable vulnerability in cancer.
  • The developed polymer-metal platform (PPS02) selectively induces necroptosis in drug-resistant cancers.
  • PPS02 shows promise as a targeted therapy that spares normal tissues, offering a potential strategy against therapy-resistant cancers.