Browsing by Author "Samtani, Suraj"
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Item MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies(2022) Rivas, Solange; Marín, Arnaldo; Samtani, Suraj; González, Evelin; Armisén, RicardoThe MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapiesItem Outcomes of Sepsis and Septic Shock in Cancer Patients: Focus on Lactate(2021) López, René; Pérez-Araos, Rodrigo; Baus, Fernanda; Moscoso, Camila; Salazar, Álvaro; Graf, Jerónimo; Montes, José Miguel; Samtani, SurajThe number of oncological patients (OP) admitted to intensive care units (ICU) for sepsis/septic shock has dramatically increased in recent years. The definition of septic shock has been modified, adding hyperlactatemia as a severity biomarker for mortality. However, it remains poorly reported in septic OP. We performed a retrospective analysis from a prospective database of sepsis/septic shock patients admitted to our ICU between September 2017 and September 2019 and followed until day 90. We identified 251 patients and 31.9% had active oncological comorbidity, mainly solid tumor (81.3%). Septic shock criteria were met for 112 (44.6%). Hyperlactatemia was observed in 136 (54.2%) patients and this was associated with a lower survival rate. Overall 90-day mortality was 15.1%. In OP vs. non-OP, hyperlactatemia was more frequent (65% vs. 49.1%, p = 0.013) and associated with lower survival (65.4% vs. 85.7%, p = 0.046). In OP, poor performance status was also associated with lower survival (HR 7.029 [1.998–24.731], p = 0.002) In an adjusted analysis, cancer was associated with lower 90-day survival (HR 2.690 [1.402–5.160], p = 0.003). In conclusion, septic OP remains a high mortality risk group in whom lactate levels and performance status could help with better risk stratification.Item Survival of Critically Ill Oncologic Patients Requiring Invasive Ventilatory Support: A Prospective Comparative Cohort Study With Nononcologic Patients(2019) López, René; Pérez-Araos, Rodrigo; Samtani, Suraj; Montes, José Miguel; Pérez, Rodrigo; Martin, María José; Salazar, Álvaro; Graf, JeronimoPurpose: Cancer is in the process of changing to become a chronic disease; therefore, an increasing number of oncologic patients (OPs) are being admitted to intensive care units (ICUs) for supportive care of disease or therapy-related complications. We compare the short- and long-term outcomes of critically ill mechanically ventilated OPs with those of their nononcologic counterparts. Patients and methods: We performed a prospective study of patients admitted to our ICU between October 2017 and February 2019. Demographic, physiologic, laboratory, clinical, and treatment data were obtained. The primary outcome was survival at 28 days and at the end of the follow-up period. Secondary outcomes were survival according to acute severity scoring (Acute Physiology and Chronic Health Evaluation II score), Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson comorbidity index. Results: A total of 1,490 patients were admitted during the study period; 358 patients (24%) were OPs, and 100 of these OPs were supported with mechanical ventilation. Seventy-three percent of OPs had an ECOG performances status of 0 or 1, and 90% had solid tumors. Reason for admission to the ICU was postoperative admission in 44 patients and neutropenic infection in 10 patients. The follow-up period was 148 days (range, 42 to 363 days). Survival at 28 days was similar between OPs and nononcologic patients and associated with the Acute Physiology and Chronic Health Evaluation II score. However, long-term survival was lower in OPs compared with nononcologic patients (52% v 76%, respectively; P < .001) and associated with poor ECOG performance status. Conclusion: Short-term survival of critically ill, mechanically ventilated OPs is similar to that of their nononcologic counterparts and is determined by the severity of the critical illness.