Browsing by Author "Cordova-Delgado, Miguel"

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    High proportion of potential candidates for immunotherapy in a Chilean cohort of gastric cancer patients: results of the FORCE1 study
    (2019) Cordova-Delgado, Miguel; Mauricio P. Pinto; Ignacio N. Retamal; Matías Muñoz-Medel; María Loreto Bravo; María F. Fernández; Betzabé Cisternas; Sebastián Mondaca; César Sanchez; Hector Galindo; Bruno Nervi; Carolina Ibáñez; Francisco Acevedo; Jorge Madrid; José Peña; Erica Koch; Maria José Maturana; Diego Romero; Nathaly de la Jara; Javiera Torres; Manuel Espinoza; Carlos Balmaceda; Yuwei Liao; Zhiguang Li; Matías Freire; Valentina Gárate-Calderón; Javier Cáceres; Gonzalo Sepúlveda-Hermosilla; Rodrigo Lizana; Liliana Ramos; Rocío Artigas; Enrique Norero; Fernando Crovari; Ricardo Armisén; Alejandro H. Corvalán; Gareth I. Owen; Marcelo Garrido
    Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.
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    Mutational Landscape and Actionable Target Rates on Advanced Stage Refractory Cancer Patients: A Multicenter Chilean Experience
    (2022) Cordova-Delgado, Miguel; Pinto, Mauricio P.; Regonesi, Carlos; Cereceda, Luis; Reyes, Jose Miguel; Itriago, Laura; Majlis, Alejandro; Rodriguez, Pablo; Fassler, Andre; Mahave, Mauricio; Leon, Maria Elisa; Gallardo, Jorge; Rodriguez, Maria Paz Z.; Berkovits, Alejandro; Manque, Patricio; Rios, Juvenal A.; Garcia-Bloj, Benjamin; Garrido, Marcelo
    Major advances in sequencing technologies and targeted therapies have accelerated the incorporation of oncology into the era of precision medicine and "biomarker-driven" treatments. However, the impact of this approach on the everyday clinic has yet to be determined. Most precision oncology reports are based on developed countries and usually involve metastatic, hard-to-treat or incurable cancer patients. Moreover, in many cases race and ethnicity in these studies is commonly unreported and real-world evidence in this topic is scarce. Herein, we report data from a total of 202 Chilean advanced stage refractory cancer patients. Retrospectively, we collected patient data from NGS tests and IHC in order to determine the proportion of patients that would benefit from targeted treatments. Overall >20 tumor types were included in our cohort and 37% of patients (n = 74) displayed potentially actionable alterations, including on-label, off-label and immune checkpoint inhibitor recommendations. Our findings were in-line with previous reports such as the cancer genome atlas (TCGA). To our knowledge, this is the first report of its kind in Latin America delivering real-world evidence to estimate the percentage of refractory tumor patients that might benefit from precision oncology. Although this approach is still in its infancy in Chile, we strongly encourage the implementation of mutational tumor boards in our country in order to provide more therapeutic options for advanced stage refractory patients.
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    Proteogenomic analysis in an early onset diffuse gastric cancer patient revealed alterations in PIK3R1, TP53, SMAD4 and a potential role of the PI3K-AKT and EGFR pathways: a case report
    (2022) Cordova-Delgado, Miguel; Pinto, Mauricio P.; Pizarro, Gonzalo; Koch, Elard; Vargas, Cristian; Hernandez, Mauricio; Nourdin, Guillermo; Saldivia, Pablo; Paz Rodriguez, Maria Z.; Berkovits, Alejandro; Manque, Patricio; Rios, Juvenal A.; Garcia-Bloj, Benjamin; Garrido, Marcelo
    Background: Early-onset gastric cancers (EOGC) are poor prognosis hard-to treat malignancies that affect young individuals (<45 years old). Case Description: Herein we describe the case of a 26-year-old female EOGC patient that initially displayed stable disease after first-line CAPOX plus immunotherapy. However, patient eventually developed progressive disease and was consecutively switched to paclitaxel plus ramucirumab, and palliative irinotecan. In search for therapeutic alternatives a proteo-genomic analysis was performed in a tissue biopsy taken after the first progression. Our analyses found a total of 18 somatic mutations, including TP53 and PIK3R1, and a previously unreported germline alteration in the tumor suppressor SMAD4. Also, our proteomic analysis found 62 proteins previously documented as ???enriched in stomach cancer??? and AKT/mTOR and EGFR as pathways with therapeutic potential. Unfortunately, the clinical utility of AKT/mTOR inhibitors or EGFR targeted therapies could not be assessed. Conclusions: As explained above EOGC is a growing health concern that affects young individuals. Furthermore, the reported case displayed a poor response to standard therapy including checkpoint inhibitors and chemotherapy despite the presence of biomarkers that predict a favorable outcome. Future studies should adopt alternative approaches to find novel, more effective therapies.