RESUMEN
Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.
Asunto(s)
Neoplasias , Inhibidores de Proteínas Quinasas , Proteínas Tirosina Quinasas Receptoras , Humanos , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Terapia Molecular DirigidaRESUMEN
This study delves into the intricate interaction between DNA and nanosystems, exploring its potential implications for biomedical applications. The focus lies in understanding the adsorption geometry of DNA when in proximity to plasmonic nanoparticles, utilizing ultrasensitive vibrational spectroscopy techniques. Employing a combined Raman-SERS analysis, we conducted an in-depth examination to clarify the molecular geometry of interactions between DNA and silver nanoparticles. Our findings also reveal distinctive spectral features regarding DNA samples due to their distinctive genome stability. To understand the subtle differences occurring between normal and cancerous DNA, their thermal stability was investigated by means of SERS measurement performed before and after a thermal treatment at 94 °C. It was proved that thermal treatment did not affect DNA integrity in the case of normal cells. On the other hand, due to epimutation pattern that characterizes cancerous DNA, variations between spectra recorded before and after heat treatment were observed, suggesting genome instability. These findings highlight the potential of DNA analysis using SERS for cancer detection. They demonstrate the applicability of this approach to overcoming challenges associated with low DNA concentrations (e.g., circulating tumor DNA) that occur in biofluids. In conclusion, this research contributes significant insights into the nanoscale behavior of DNA in the presence of nanosystems.