Predictive Value and Therapeutic Significance of Somatic BRCA Mutation

Frederic Pont^*
*Correspondence: Frederic Pont, Department of Human Genome, Gadjah Mada University, Bulaksumur, Sleman, Indonesia, Email:

Keywords

BRCA mutation • Pancreatic cancers • Non-germline cells

Introduction

Somatic BRCA mutations serve as important predictive biomarkers in cancer diagnosis, prognosis, and treatment response. These mutations are associated with an increased risk of cancer development and are indicative of genomic instability within tumor cells. Several studies have demonstrated the prognostic significance of somatic BRCA mutations across various cancer types. For instance, in ovarian cancer, patients with somatic BRCA mutations often exhibit a better response to platinum-based chemotherapy and have improved survival outcomes compared to those without these mutations. Similarly, in breast cancer, somatic BRCA mutations have been linked with aggressive tumor characteristics and poorer prognosis. Furthermore, somatic BRCA mutations also influence treatment response and guide therapeutic decisions. Tumors harboring somatic BRCA mutations are more sensitive to DNA-damaging agents, such as platinum-based chemotherapy and PARP inhibitors [1-3]. This heightened sensitivity is attributed to the concept of synthetic lethality, wherein the presence of BRCA mutations renders cancer cells vulnerable to specific DNA repair pathways. Therefore, identifying somatic BRCA mutations aids in selecting appropriate treatment regimens and predicting the efficacy of targeted therapies.

Literature Review

The therapeutic significance of somatic BRCA mutations lies in their utility as predictive biomarkers for targeted therapies, particularly PARP inhibitors. PARP inhibitors exploit the concept of synthetic lethality by selectively targeting cancer cells with defective DNA repair mechanisms, such as those harboring BRCA mutations. Clinical trials have demonstrated the efficacy of PARP inhibitors, such as olaparib, niraparib, and rucaparib, in treating various cancers with somatic BRCA mutations, including ovarian, breast, and pancreatic cancers. Moreover, somatic BRCA mutations also influence the response to conventional chemotherapy agents, particularly platinum-based drugs. Tumors with somatic BRCA mutations exhibit heightened sensitivity to platinum compounds due to impaired DNA repair mechanisms, leading to increased DNA damage and cell death. Therefore, incorporating platinumbased chemotherapy in the treatment regimens of cancers with somatic BRCA mutations has shown improved clinical outcomes.

Discussion

Additionally, somatic BRCA mutations hold promise in the realm of immunotherapy. Recent studies have highlighted the potential synergy between immune checkpoint inhibitors and BRCA mutations, particularly in tumors with microsatellite instability or high tumor mutational burden. Somatic BRCA mutations contribute to the generation of neoantigens, enhancing tumor immunogenicity and promoting antitumor immune responses [4,5]. Therefore, exploring the combination of immunotherapy with PARP inhibitors or platinumbased chemotherapy in cancers harboring somatic BRCA mutations represents an intriguing avenue for future research.

Despite the promising therapeutic implications of somatic BRCA mutations, several challenges exist in their clinical implementation. One such challenge is the identification of somatic BRCA mutations through routine clinical testing. Current diagnostic methods primarily focus on germline BRCA testing, necessitating the development of reliable and cost-effective techniques for detecting somatic mutations in tumor samples. Moreover, resistance mechanisms to targeted therapies, such as PARP inhibitors, pose significant obstacles in the management of cancers with somatic BRCA mutations. Elucidating the molecular mechanisms underlying drug resistance and exploring combination strategies to overcome resistance are essential for optimizing treatment outcomes [6].

Future directions in somatic BRCA research encompass several areas, including the integration of genomic profiling into routine clinical practice, the development of novel targeted therapies, and the exploration of combination treatment strategies, including immunotherapy and targeted agents. Additionally, collaborative efforts involving clinicians, researchers, and pharmaceutical companies are crucial for advancing the field and translating scientific discoveries into clinical benefits for patients.

Conclusion

Somatic BRCA mutations hold substantial predictive value and therapeutic significance in cancer management. These mutations not only inform prognosis and treatment response but also guide therapeutic decisions, particularly in the era of precision medicine. By leveraging the predictive and therapeutic implications of somatic BRCA mutations, personalized treatment approaches can be tailored to individual patients, thereby improving clinical outcomes and enhancing the quality of cancer care. Continued research efforts aimed at unraveling the complexities of somatic BRCA mutations and exploring innovative treatment strategies are essential for realizing the full potential of these biomarkers in oncology practice.

Acknowledgement

None.

Conflict of Interest

There are no conflicts of interest by author.

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