Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

7.8K
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...
7.8K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Total synthesis of γ-tocopherol <i>via</i> asymmetric 1,4-conjugate addition of alkyl Grignard reagents to 2-methyl chromone.

Organic & biomolecular chemistry·2026
Same author

Highly Regio- and Enantioselective Catalytic 1,6-Conjugate Addition of Grignard Reagents to Cyclic Dienones.

Organic letters·2026
Same author

A Personalized Therapeutic Approach for Liver Cancers Expressing the African-Centric P47S Variant of TP53.

Molecular cancer research : MCR·2026
Same author

Harnessing Unique Boron Chemistry to Develop a New Class of Non-hydroxamate HDAC Inhibitors with Validated In Vivo Efficacy.

Journal of medicinal chemistry·2026
Same author

NN-01-195, a novel conjugate of HSP90 and AURKA inhibitors, effectively targets solid tumors.

Molecular cancer therapeutics·2026
Same author

Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer.

Cancer research·2025

Related Experiment Video

Updated: Aug 11, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.6K

Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer.

Clare M Adams1, Ramkrishna Mitra1, Youcai Xiao2

  • 1Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

Cancer Discovery
|February 3, 2023
PubMed
Summary

A novel PROteolysis TArgeting Chimera (PROTAC) drug effectively targets MDM2, a protein crucial for triple-negative breast cancer (TNBC) survival. This breakthrough therapy induces cancer cell death while sparing healthy cells, offering a promising new treatment for aggressive TNBC.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.3K
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

15.1K

Related Experiment Videos

Last Updated: Aug 11, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.6K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.3K
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

15.1K

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Triple-negative breast cancer (TNBC) often inactivates the p53 tumor suppressor, leading to increased aggressiveness and resistance to therapies.
  • p53-inactivated TNBC represents a significant unmet medical need due to its aggressive nature and poor prognosis.

Purpose of the Study:

  • To identify and exploit a novel protein vulnerability in p53-inactivated TNBC.
  • To design and evaluate a targeted therapeutic agent for p53-inactivated TNBC.

Main Methods:

  • Development of a PROteolysis TArgeting Chimera (PROTAC) designed to selectively degrade MDM2.
  • Assessment of PROTAC efficacy in 2D/3D cell cultures, patient explants, and TNBC xenograft mouse models.
  • Transcriptomic analysis and investigation of downstream signaling pathways, including p53 family members.

Main Results:

  • The developed MDM2-PROTAC selectively induced proteasomal degradation of MDM2 in p53-inactivated TNBC cells.
  • MDM2 degradation resulted in apoptosis of TNBC cells, including those from relapsed tumors, while sparing normal cells.
  • In vivo studies demonstrated on-target efficacy, significant tumor reduction, extended survival, and no observed toxicity in mice.
  • Activation of TAp73 was identified as essential for mediating PROTAC-induced apoptosis.

Conclusions:

  • MDM2 is essential for the survival of p53-inactivated TNBC cells, contrary to the traditional p53/MDM2 paradigm.
  • PROTAC-mediated MDM2 degradation represents a novel and potentially superior therapeutic strategy for TNBC compared to existing MDM2 inhibitors.
  • This approach offers a promising new avenue for treating aggressive and therapy-resistant TNBC.