In June 2024, the National Medical Products Administration approved the first PARP inhibitor combination therapy based on a BRCA2 mutation companion diagnostic, marking a major advancement in the application of the “synthetic lethality” concept in solid tumor treatment. A recent Nature Medicine study demonstrated that using BRCA1/2 knockout models in preclinical validation systems can increase the success rate of PARP inhibitor screening by 40%. This breakthrough injects new momentum into the development of personalized anti-cancer therapies.
PARP and BRCA1/2: The “Golden Duo” of DNA Repair
The PARP (poly ADP-ribose polymerase) family plays a central role in DNA damage repair (Figure 1). PARP1/2 initiate base excision repair by recognizing single-strand breaks, while BRCA1/2 proteins govern homologous recombination repair (HRR)—these two mechanisms act as the cell’s “double safety net.” When BRCA1/2 genes undergo loss-of-function mutations, the HRR pathway collapses. Inhibiting PARP at this point results in lethal accumulation of DNA damage, which lies at the heart of synthetic lethality.
BRCA2 mutation carriers face a 45–84% increased risk of developing breast cancer and an 11–27% risk of ovarian cancer. PARP inhibitors exploit synthetic lethality to selectively kill these defective cells and have been approved for ovarian, breast, and prostate cancer indications. Notably, around 50% of HRR-deficient tumors exhibit epigenetic silencing rather than BRCA2 mutations, opening new avenues for expanded therapeutic applications.
In recent years, the use of PARP inhibitors in oncology has rapidly expanded—from initial approval for breast cancer to broader indications including ovarian, pancreatic, and prostate cancers. These inhibitors offer a precise targeted treatment option for various malignancies, disrupting traditional treatment paradigms. With the broadening of indications, the global PARP inhibitor market reached USD 2.4 billion in 2020 and is projected to grow to USD 12.3 billion by 2025, with a compound annual growth rate of 38.3%.
Currently, five PARP inhibitors are approved in China: olaparib, niraparib, fluzoparib, pamiparib, and talazoparib. Additionally, over 20 other PARP inhibitors are in development. Among them, Junpai Yingshi Pharma’s senaparib has filed for marketing approval and is expected to launch in Q4 2025. Chia Tai Tianqing’s TQB3823 and AstraZeneca’s saruparib are currently in Phase III clinical trials, likely expanding treatment options further in the future.
To support the development of targeted PARP inhibitors, Kyinno Biotechnology, leveraging its robust engineered cell development platform, has constructed BRCA2-/- tumor cell lines using CRISPR/Cas9 technology. In vitro and in vivo validation data are summarized below. Please contact us for more information.
BRCA-KO cell line list:
- KC-4344 HCT116-BRCA1-KO
- KC-4347 HCT116-BRCA2-KO
- KC-4587 A549-BRCA1-KO
- KC-4759 DLD1-BRCA2-KO
- KC-4556 EMT6-mouse-BRCA2-KO
In vivo validation of HCT116-BRCA2-KO model
In vivo validation of DLD1-BRCA2-KO model
In vitro pharmacodynamic validation of BRCA-KO models
