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

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

7.6K
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...
7.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

3.3K
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...
3.3K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

4.9K
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...
4.9K

You might also read

Related Articles

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

Sort by
Same author

Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer.

Research square·2026
Same author

Treatment Patterns and Attrition in Metastatic Castration-Resistant Prostate Cancer.

JAMA network open·2026
Same author

Case of complete response to immunotherapy in MMR-deficient prostate cancer associated with NK-like and CD4<sup>+</sup>CD8<sup>+</sup> T cells.

Cell reports. Medicine·2026
Same author

ERK builds a population of short-lived nascent adhesions that produce persistent edge protrusion and cell migration.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Clinical applications of PARP inhibitors in breast, ovarian, and prostate cancer: current insights and future directions.

Clinical advances in hematology & oncology : H&O·2026
Same author

The 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) study.

BJU international·2026

Related Experiment Video

Updated: Jul 8, 2025

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.1K

Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in

Jacob J Orme1, Fadi Taza2, Navonil De Sarkar3

  • 1Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.

European Urology Oncology
|December 10, 2023
PubMed
Summary

Patients with BRCA2 and SPOP mutations receiving poly (ADP-ribose) polymerase (PARP) inhibitors showed improved outcomes in metastatic castration-resistant prostate cancer. This suggests SPOP mutations may enhance PARP inhibitor efficacy in BRCA2-altered mCRPC.

Keywords:
BRCA2 mutationPoly(ADP-ribose) polymerase inhibitorsSPOP mutation

More Related Videos

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.1K
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

8.7K

Related Experiment Videos

Last Updated: Jul 8, 2025

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.1K
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.1K
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

8.7K

Area of Science:

  • Oncology
  • Genetics
  • Cancer Research

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) with BRCA2 mutations responds to PARP inhibitors.
  • Additional biomarkers are needed to predict PARP inhibitor efficacy in mCRPC.
  • Preclinical data suggest SPOP inactivation may enhance PARP inhibitor sensitivity.

Purpose of the Study:

  • To investigate if SPOP mutations predict enhanced PARP inhibitor response in BRCA2-altered mCRPC.
  • To compare clinical outcomes in patients with BRCA2 mutations with and without concurrent SPOP mutations treated with PARP inhibitors.

Main Methods:

  • Multicenter retrospective study of 131 patients with BRCA2-altered mCRPC treated with PARP inhibitors.
  • Compared outcomes (PSA response, PFS, OS) between patients with BRCA2mut/SPOPmut (n=14) and BRCA2mut/SPOPwt (n=117) disease.
  • Used multivariable Cox proportional hazard models adjusting for clinical and genomic factors.

Main Results:

  • Patients with BRCA2mut/SPOPmut disease showed higher PSA response rates (86% vs 60%) and longer median treatment duration (24.0 vs 8.0 months).
  • Multivariable analysis revealed significantly longer PSA-PFS (adjusted HR 0.16), clinical/radiographic PFS (adjusted HR 0.28), and OS (adjusted HR 0.19) for BRCA2mut/SPOPmut patients.
  • Genomic analysis indicated higher HRR defect scores in BRCA2mut/SPOPmut disease.

Conclusions:

  • Co-alteration of BRCA2 and SPOP predicts superior outcomes with PARP inhibitor therapy in mCRPC compared to BRCA2 alteration alone.
  • The enhanced efficacy may be linked to increased homologous recombination repair (HRR) defects in patients with both mutations.
  • Further prospective validation is warranted.