Related Experiment Video
Updated: Feb 27, 2026
Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model
Published on: February 17, 2019
Paraptosis Turning Cellular Stress into Therapeutic Weapon for Urological Diseases
Jie Wang1,2, Qi Zhang1, Chuanzan Zhou1
1Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.
Abstract:
Drug resistance and impaired apoptosis limit durable responses in urological malignancies. Paraptosis is a regulated, nonapoptotic cell death program marked by prominent cytoplasmic vacuolization, typically driven by endoplasmic reticulum (ER) swelling and mitochondrial dysfunction. This perspective synthesizes emerging evidence in prostate, bladder, and renal cancers and proposes a stress-axis framework in which diverse inducers converge into 3 mechanistic classes: (a) proteostasis disruptors that precipitate acute ER stress, (b) ion-handling modulators that trigger lethal mitochondrial Ca2+ overload, and (c) redox regulators that amplify reactive-oxygen-species-driven proteotoxic stress. We discuss how natural products, repurposed agents, and delivery platforms can be integrated with chemotherapy, targeted therapy, or immunotherapy to overcome resistance and exploit death-pathway cross talk. Key translational priorities include defining pathway-specific biomarkers, mapping ER-mitochondrion signaling thresholds, and dissecting stress-buffering and cytoprotective autophagy as resistance mechanisms. Clarifying these principles may enable the context-specific exploitation of paraptosis across urological cancers and related diseases, in both primary and therapy-refractory settings.
Insights
Paraptosis, a cell death pathway, offers new strategies against drug-resistant urological cancers. Understanding its mechanisms can help overcome treatment resistance in prostate, bladder, and kidney cancers.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Drug resistance and apoptosis evasion hinder effective treatment in urological cancers.
- Paraptosis is a distinct regulated cell death pathway characterized by cytoplasmic vacuolization, endoplasmic reticulum (ER) swelling, and mitochondrial dysfunction.
Purpose of the Study:
- To synthesize evidence on paraptosis in prostate, bladder, and renal cancers.
- To propose a stress-axis framework for understanding paraptosis induction.
- To explore therapeutic strategies for exploiting paraptosis to overcome resistance.
Main Methods:
- Literature synthesis and evidence-based perspective.
- Categorization of paraptosis inducers into three mechanistic classes: proteostasis disruption, ion-handling modulation, and redox regulation.
- Discussion of therapeutic integration with existing cancer treatments.
Main Results:
- Diverse inducers of paraptosis converge via ER stress, mitochondrial calcium overload, or reactive oxygen species.
- Natural products, repurposed drugs, and novel delivery platforms show potential for paraptosis induction.
- Autophagy can act as a resistance mechanism by buffering cellular stress.
Conclusions:
- A stress-axis framework clarifies paraptosis induction in urological malignancies.
- Targeting paraptosis offers a promising avenue to overcome therapeutic resistance.
- Further research into biomarkers and resistance mechanisms is crucial for clinical translation.
Related Concept Videos
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:30Apoptosis
01:25Urinary Tract Infection II: Pathophysiology
01:13The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:18The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...