Avaliação da heterogeneidade de vias de sinalização ativadas por receptores de tirosina quinase em câncer de mama

Abstract

Tyrosine Kinase Receptors (RTKs) are cell membrane receptors that mediate the transition and activation of various intracellular signals. Among the signaling pathways activated by RTKs are mitogen-activated protein kinase (MAPK), Janus kinase (JAK), and phosphoinositide 3-kinase (PI3K), which are responsible for cell growth, proliferation, survival, and migration. Due to their role in regulating fundamental cellular processes, alterations in RTK-activated pathways are frequently associated with cancer. Breast cancer is the most common neoplasm among women worldwide, and many patients exhibit resistance to the drugs used in treatment, negatively impacting therapeutic responses. Various mechanisms are involved in the resistance process, among them tumor heterogeneity. Heterogeneity can be inter- or intratumoral, resulting in the adaptation and survival of cells to received stimuli, such as chemotherapy, for example. Therefore, investigating tumor heterogeneity is essential in identifying and developing better treatments for cancer. Thus, the aim of this study is to evaluate the heterogeneity of signaling pathways activated by RTKs in breast cancer, through bioinformatic analysis of available databases. The results demonstrate that gene expression within the same tumor is highly variable, with some cells exhibiting high expression while others show absent expression,highlighting intratumoral heterogeneity. ER+ tumors displayed greater homogeneity in gene expression, whereas HER2+ and triple-negative subtypes exhibited more diverse patterns, reflecting differences in tumor biology. Moreover, the differential activation of these pathways suggests their potential role in tumor progression and therapeutic resistance. Therefore, it is concluded that analyzing tumor heterogeneity is essential for understanding the complexity of breast cancer, and that approaches such as single-cell sequencing may contribute to the development of more effective and personalized therapies.