Related Experiment Video
Updated: May 15, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Therapeutic advances and application of PARP inhibitors in breast cancer
1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
Abstract:
Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cells vulnerable to inhibition of DNA repair related proteins, such as PARP1. Pre-clinical studies has demonstrated that cancer cells with BRCA1/2 deficient are sensitive to PARPi, which are an emerging class of small molecule drug. Several clinical trials demonstrated the promising efficacy of PARP inhibitors for BRCA1/2 mutated breast cancer patient through selectively induce synthetic lethality cancer cells. Currently, four PARP inhibitors had been approved by FDA for clinical use. PARPi demonstrated to improve progression-free survival, while resistance to PARPi is inevitable. In this review article, we highlighted the advances in the PARPi clinical trials, resistance mechanism and coping strategies in breast cancer patients. We also summarized the international guideline and recommendations on PARP inhibitor usage in breast cancer.
Insights
PARP inhibitors offer a promising treatment for BRCA1/2-mutated breast cancer by exploiting DNA repair deficiencies. However, resistance to these drugs is inevitable, necessitating strategies to overcome it.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- BRCA1/2 genes are crucial for the homologous recombination repair (HRR) pathway.
- Mutations in BRCA1/2 lead to DNA damage response (DDR) deficiency and genomic instability.
- This deficiency sensitizes cancer cells to DNA repair inhibitors like PARP inhibitors (PARPi).
Purpose of the Study:
- To review advances in PARP inhibitor (PARPi) clinical trials for BRCA1/2-mutated breast cancer.
- To discuss mechanisms of PARPi resistance and strategies to overcome it.
- To summarize international guidelines for PARPi usage in breast cancer.
Main Methods:
- Literature review of pre-clinical studies and clinical trials on PARPi in breast cancer.
- Analysis of resistance mechanisms and coping strategies.
- Synthesis of current international treatment guidelines.
Main Results:
- PARPi demonstrate efficacy in BRCA1/2-mutated breast cancer, improving progression-free survival.
- Four PARPi are FDA-approved for clinical use.
- Resistance to PARPi is a significant clinical challenge.
Conclusions:
- PARPi represent a key therapeutic strategy for BRCA1/2-mutated breast cancer.
- Understanding and overcoming PARPi resistance is critical for long-term patient benefit.
- Adherence to international guidelines ensures optimal use of PARPi.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:34Inhibition of Cdk Activity
02:50Combination Therapies and Personalized Medicine
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...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...