Related Experiment Video

Updated: Apr 27, 2026

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

8.3K

BRCA2 inhibition enhances cisplatin-mediated alterations in tumor cell proliferation, metabolism, and metastasis

Mateusz Rytelewski1, Jessica G Tong2, Adrian Buensuceso3

  • 1Department of Microbiology and Immunology, Western University, London, Ontario, Canada.

Molecular Oncology
|June 30, 2014
PubMed

Insights

Targeting BRCA2 DNA repair with antisense oligonucleotides (ASO) enhances cisplatin chemotherapy efficacy in various cancers. This BRCA2 ASO combination therapy shows promise for treating ovarian, lung, and breast cancers, reducing metastasis and improving patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor cells exhibit genomic instability, impacting DNA repair and therapeutic response.
  • BRCA2, a key player in homologous recombination repair, is linked to cancer risk and patient survival.
  • Targeting DNA repair pathways presents a promising strategy for cancer therapy.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting BRCA2 in cancer treatment.
  • To evaluate a novel BRCA2-targeting antisense oligonucleotide (ASO) in combination with cisplatin.
  • To assess the impact of BRCA2 ASO on cancer cell sensitivity, resistance, metastasis, and cellular metabolism.

Main Methods:

  • Analysis of TCGA data to correlate BRCA2 alterations with patient survival in ovarian and endometrial cancers.
  • Development and testing of a second-generation BRCA2-targeting antisense oligonucleotide (ASO).
  • In vitro assessment of cancer cell sensitivity to cisplatin with and without BRCA2 ASO, including acquired resistance models.
  • In vivo studies to evaluate the effect of BRCA2 ASO and cisplatin on metastatic frequency.
  • Analysis of cellular respiration and glucose metabolism in response to combination therapy.

Main Results:

  • BRCA2 alterations were associated with increased survival in ovarian and endometrial cancer patients.
  • BRCA2 ASO sensitized lung, ovarian, and breast cancer cells to cisplatin by up to 60%.
  • BRCA2 ASO resensitized cisplatin-resistant head and neck cancer cells and minimally affected non-tumor cells.
  • Combination therapy reduced metastatic frequency in vivo by 77%.
  • BRCA2 ASO plus cisplatin decreased cellular respiration and increased glucose uptake, preceding cell death.

Conclusions:

  • BRCA2 plays a significant role in regulating cancer cell metastasis and metabolic response to cisplatin.
  • BRCA2 ASO in combination with cisplatin demonstrates potential as an effective anti-cancer therapeutic strategy.
  • This approach offers a targeted method to enhance chemotherapy efficacy and overcome resistance.
Keywords:
BRCA2CisplatinDNA repairDrug sensitizationmetabolismmetastasis

More Related Videos

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

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

Published on: August 12, 2015

8.8K
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA108:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

16.2K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
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...
7.0K
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...
2.6K
Abnormal Proliferation02:23

Abnormal Proliferation

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...
4.0K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
8.5K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...
2.3K