Related Experiment Video

Updated: Dec 7, 2025

Evaluating In Vitro DNA Damage Using Comet Assay
10:43

Evaluating In Vitro DNA Damage Using Comet Assay

Published on: October 11, 2017

39.0K

An olaparib window-of-opportunity trial in patients with early-stage endometrial carcinoma: POLEN study

Ignacio Romero1, M Jesús Rubio2, Manuel Medina2

  • 1Instituto Valenciano de Oncología, Valencia, Spain.

Gynecologic Oncology
|September 29, 2020
PubMed
Abstract

Insights

Olaparib significantly reduced cyclin D1 expression in endometrial cancer (EC) patients, particularly those with ARID1A-deficient tumors. This poly(ADP-ribose) polymerase (PARP) inhibitor also decreased GLUT1 activity, suggesting potential for targeted EC treatment strategies.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Endometrial cancer (EC) is a significant gynecologic malignancy.
  • Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, shows potential in treating EC.
  • Understanding olaparib's molecular effects in EC is crucial for treatment optimization.

Purpose of the Study:

  • To evaluate the effects of olaparib on EC biomarkers.
  • To assess changes in cell cycle-related proteins (cyclin D1, Ki67, cleaved caspase-3) following olaparib treatment.
  • To explore the correlation between olaparib, PARP-1 levels, ARID1A status, and GLUT1 activity in EC.

Main Methods:

  • A window-of-opportunity trial involving 31 operable EC patients receiving neoadjuvant olaparib (300mg BID for 28 days).
  • Tissue samples analyzed at baseline and post-treatment for protein expression (cyclin D1, Ki67, cleaved caspase-3) via immunostaining.
  • Biomarker analysis included PARP-1 levels, ARID1A status, and plasma olaparib concentrations correlated with GLUT1 activity.

Main Results:

  • Olaparib significantly inhibited cyclin D1 expression (p < 0.01), but not Ki67 or cleaved caspase-3.
  • PARP-1 levels positively correlated with cyclin D1 levels (rho = 0.661, p = 0.0001).
  • Both PARP-1 and cyclin D1 were significantly lower in ARID1A-deficient tumors.
  • A significant inverse relationship was observed between plasma olaparib concentrations and GLUT1 activity (r = -0.5885, p < 0.05).
  • Most toxicities were gastrointestinal and grade 1-2.

Conclusions:

  • Olaparib effectively reduces cyclin D1 expression in EC, with enhanced effects in ARID1A-deficient tumors.
  • Olaparib treatment leads to decreased GLUT1 plasma activity.
  • These findings support olaparib-based strategies for specific EC patient populations, potentially improving treatment prediction.
Keywords:
Corpus uteri cancerEndometrioid carcinomaOlaparibPARP inhibitorType I endometrial carcinoma

More Related Videos

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays04:07

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Published on: February 24, 2023

2.0K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

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

Published on: July 25, 2020

7.6K

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...
3.6K
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.4K
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...
8.4K
Clinical Trials01:16

Clinical Trials

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
10.0K