BRCA1 Mutations and Their Consequences in Multiple Cancers: Molecular Insights and Emerging Therapeutic Strategies

Abstract: Cancer is a global health burden, contributing significantly to the rising mortality rates across various forms of the disease. Identifying the underlying cause of this ailment is crucial to finding a way to save numerous lives worldwide. The BRCA1, a well-recognised tumor suppressor gene located on chromosome 17q12, plays a vital role in numerous cancers, including breast, ovarian, cervical, prostate, lung, colorectal, gastric, and bladder cancers. Mutations in the BRCA1 gene can lead to loss of its tumor-suppressor function, significantly increasing the risk of developing various malignancies. The BRCA1 protein is involved in cell cycle control, ubiquitination, transcription regulation, and DNA repair through homologous recombination. Individuals carrying BRCA1 mutations are at high risk of developing breast and ovarian cancers. Genetic testing has become a crucial tool for the management of cancer as well as prevention strategies. A mutation in BRCA1 can affect overall survival outcomes, and its overexpression may influence poor treatment outcomes in cervical cancer. In prostate cancer, BRCA1 mutations are associated with a more aggressive disease phenotype and poorer survival outcomes. In lung cancer, a BRCA1 mutation could result in homologous recombination deficiency and reduced protein function. Some studies highlighted the pathogenicity of BRCA1 mutations in non-small cell lung cancer. Colorectal, gastric, and bladder cancer also demonstrate significant association with BRCA1 mutations, along with increased risk and poorer survival outcomes. Targeted therapeutic approaches, such as poly (ADP-ribose) polymerase inhibitors (PARPi), have shown promising results in targeting BRCA1-mutated cancers by exploiting the concept of synthetic lethality. As research continues to unravel the complexities of BRCA1-linked cancers, novel targeted therapies are being developed to enhance treatment outcomes and improve patient prognosis, particularly when combined with chemotherapy agents and radiation therapy. In this review, we discuss the current status of BRCA1 in various types of cancers, as well as the challenges and opportunities in BRCA1-mutated cancer cases.