Related Experiment Video

Updated: Jul 4, 2026

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
12:55

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

Die hard: when cells refuse apoptosis-the rise of paraptosis and other death pathways

Cecilia Anceschi1, Elena Frediani1, Jessica Ruzzolini1

  • 1Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Cell Death Discovery
|June 29, 2026
PubMed

Insights

Cancer cells can switch between paraptosis-sensitive and -resistant states, a plasticity that drives therapeutic resistance. Understanding this regulated cell death (RCD) mechanism offers new precision targeting strategies for difficult-to-treat cancers.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Therapeutics

Background:

  • Resistance to apoptosis is a significant challenge in cancer treatment.
  • Paraptosis, a form of regulated cell death (RCD), presents a potential therapeutic vulnerability in apoptosis-refractory tumors.
  • Limited understanding of paraptosis regulation within tumor ecosystems hinders its therapeutic application.

Purpose of the Study:

  • To introduce the concept of paraptotic plasticity in cancer cells.
  • To explore the molecular mechanisms and environmental factors influencing paraptotic plasticity.
  • To discuss potential therapeutic strategies, including nanotechnology, to exploit paraptotic vulnerabilities.

Main Methods:

  • Review of existing literature on paraptosis, apoptosis resistance, and tumor microenvironment.
  • Analysis of molecular determinants of paraptosis, including ER stress, mitochondrial function, and proteotoxic stress.
  • Discussion of the role of microbiota-derived metabolites and nanotechnology in modulating paraptosis.

Main Results:

  • Cancer cells exhibit "paraptotic plasticity," reversibly switching between sensitivity and resistance to paraptosis.
  • This plasticity is influenced by metabolic stress, therapeutic pressure, and tumor microenvironmental cues.
  • Key molecular factors like ER stress, mitochondrial dysfunction, ion homeostasis, and proteotoxic stress regulate paraptotic outcomes.

Conclusions:

  • Paraptotic plasticity represents a novel mechanism of therapeutic resistance in cancer.
  • Targeting paraptotic vulnerabilities offers a promising avenue for precision oncology.
  • Nanotechnology-based strategies can be developed to overcome resistance in challenging cancers by leveraging paraptotic plasticity.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Related Concept Videos

Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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 20th century...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...