Mol Cell: Scientists have identified a key driving protein that cancer cells develop resistance to therapy.

October 6, 2020 // -- Individuals with BRCA1/2 mutations have a higher risk of breast, ovarian and prostate cancer, and cancer becomes more aggressive when patients become resistant to life-saving treatments In a recent study published in the international journal Molecular Cell, scientists from the University of Texas at Austin and others identified a key driver of cancer cell tolerance to drugs, which may help develop new targeted cancer therapies.
Photo Source: NiH researcher Dr Kyle Miller says one of the main problems in cancer treatment today is the occurrence of drug resistance, which is often life-threatening when therapy stops working in the patient's body, so understanding the molecular mechanisms of cancer resistance is especially important for scientists.
In this study, researchers found a specific protein that may help clinicians predict which patients will become resistant to a class of drugs commonly used to treat BRCA1/2 missing tumors, and the findings could help researchers develop more effective treatment plans for cancer patients.
This special protein called PCAF promotes DNA damage in cancer cells with BRCA1/2 mutations, while patients with low levels of PCAF protein tend to have poor prognosis and are more susceptible to the treatment of PARP inhibitors, which are commonly used to treat tumors with BRAC deficiency.
researchers say the development of PARP inhibitors is a major breakthrough in the treatment of these malignant cancers, when the body's PCAF protein levels are low, it will actually protect cancer cells from drug damage, by testing live tissue samples, researchers can use PCAF protein as a molecular marker to evaluate the response of PARP inhibitors, so as to assess which treatment is most effective in treating cancer patients.
Fortunately, there is another drug called HDAC inhibitors that can enhance the effectiveness of PCAF proteins, and HDAC inhibitors and PARP inhibitors may potentially be combined into a new combination therapy, researcher Miller said, after previous studies have shown that the two drugs work together perfectly;
researchers point out that revealing how PCAF works can provide clues to later scientists' resistance to cancer, and that PCAF proteins are primarily responsible for modifying chromosomes, which can assemble 6 feet of DNA into the nucleation of each cell, so PCAF may also provide some research clues and insights into the mechanisms of cell replication. Miller, the
final researcher, said the focus of this study is to understand chromatin and its effects on replicated DNA, and how chromatin protects DNA and controls its entry and exit from the nuclei of cells;
() Original source: Jae Jin Kim, Seo Yun Lee, Ji-Hye Choi, et al. PCAF-Mediated Histone Acetylation Promotes Replication Fork Fork By MRE11 and EXO1 in BRCA-Deficient Cells, Molecular Cell (2020). DOI:10.1016/j.molcel.2020.08.018.