Mutations in Necroptosis-Related Genes Reported in Breast Cancer: A Cosmic and Uniport Database-Based Study

Breast cancer (BC) now holds the top position as the primary reason of cancer-related fatalities worldwide, overtaking lung cancer. BC is classified into diverse categories depending on histopathological type, hormone receptor status, and gene expression profile, with ongoing evolution in their classifications. Cancer initiates and advances when there is a disruption in cell death pathways. In BC, the primary cell death pathway, apoptosis, experiences dysregulation across multiple stages. Ongoing studies aim to discover therapeutic targets that enhance cancer cell susceptibility to apoptosis. However, resistance to this therapy remains a significant challenge in treating BC. If apoptosis is hindered, investigating alternative pathways for cell death that can effectively eradicate BC cells during treatment becomes a valuable endeavor. In this context, necroptosis is gaining considerable focus as an alternative cell death pathway. Necroptosis represents a programmed version of necrosis which shares its key regulators with apoptosis. When apoptosis is hampered, necroptosis serves as an alternative cell death pathway even in physiological conditions like formation of limbs during embryonic development. Additionally, it comes into play during bacterial and viral infections when the apoptosis machinery is hijacked and inhibited by proteins from these pathogens. Studies reveal that in BC, mutations significantly impact molecules in the apoptosis pathway, contributing to the onset, advancement, and multiplication of cancer cells. Although some studies do indicate that the functionality of necroptosis pathway may be compromised in malignancy the status of its key molecules remains largely unknown. In this article, we aim to gather the known mutations present in key molecules of necroptosis among various subtypes of BC, utilizing data from the Cosmic and UniProt databases. The same may help to enhance the development of therapeutic strategies to effectively induce necroptosis in apoptosis-resistant BCs.