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Revisiting potential role of metformin in the circRNA-miRNA-mRNA axis: translational medicine perspectives in gastrointestinal cancer
(Springer Science and Business Media LLC, 2026-04-02)
Juan A. Godoy
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Juvenal A. Ríos
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Tomás de Mayo
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Jenny F. Henríquez
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Cristopher San Martin Abello
2
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Abstract 6440: Effects of cumulative tobacco exposure on lung cancer genomic profiles in Latin Americans
(American Association for Cancer Research (AACR), 2026-04-03)
Javiera Garrido
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Evelin González
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Alejandro Blanco
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Gonzalo Sepúlveda-Hermosilla
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Matias Freire
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Motivation:</jats:title> <jats:p>Tobacco exposure is a major determinant of tumor genomic landscapes in non-small cell lung cancer (NSCLC). Two of the most clinically relevant actionable genes in lung cancer, EGFR and KRAS, show opposite patterns, with smokers exhibiting a higher prevalence of alterations in KRAS and never-smokers in EGFR. Yet, the dynamic and evolution of genomic changes as a function of cumulative tobacco exposure has received limited attention. Here, we examine how tumor genomic profiles vary according to smoking intensity, duration, and time since cessation (TSC). Our study focuses on an underrepresented population of Latin American patients, where additional research is needed to better characterize tumor heterogeneity.</jats:p> </jats:sec> <jats:sec> <jats:title>Methodology:</jats:title> <jats:p>The population was obtained from the protocol Characterization and Validation of Molecular Diagnostic Technologies for Lung Cancer Patients from Chile, Brazil, and Peru. Participant recruitment was between July 2015 and October 2018 across 37 different centers. Primary or metastatic NSCLC specimens were analyzed, and genomic profiles were generated with the Oncomine Focus Assay (OFA). A total of 1,864 participants yielded QC-approved genomic profiles. Covariates of interest were assessed at enrollment. Cumulative tobacco exposure, including smoking intensity (cigarettes per day), duration, and TSC, was quantified using the Comprehensive Smoking Index (CSI). In addition, smoking status (current vs. never) was recoded as a function of TSC in order to identify the time period during which major genomic alterations (GA) are most likely to occur. Descriptive statistics, generalized linear models, and generalized additive models were used to evaluate the association between CSI and the prevalence of GA across genes. All models were adjusted for potential confounders, including country, age, sex, NSCLC subtype, cancer stage and history of cancer.</jats:p> </jats:sec> <jats:sec> <jats:title>Results and Conclusions:</jats:title> <jats:p>A total of 1100 patients had complete genomic and tobacco exposure information. Among current smokers, median smoking intensity and duration were 20 cigarettes per day and 48 years, respectively, compared with 30 cigarettes per day and 47 years among former smokers. Ninety percent of former smokers had ceased tobacco use at least 10 years prior to diagnosis, with a median TSC of 1 year. CSI analysis identified 14 genes significantly associated with genomic alteration status, including EGFR, PIK3CA, ALK, MTOR, ERBB3, and RET. Higher CSI values (4th quartile) showed approximately double the frequency of genomic alterations compared with the lowest CSI quartile for ALK (16.2% vs. 8.7%), RET (12.8% vs. 6.9%), and MTOR (15% vs. 6.9%). Mid-range CSI values exhibited the lowest prevalence of alterations in EGFR (12.6% vs. 31%) and PIK3CA (6.9% vs. 14.5%). Overall, these findings support the value of CSI in refining exposure-genotype associations and the need for improves risk stratification efforts in diverse populations.</jats:p> </jats:sec> <jats:sec> <jats:title>Citation Format:</jats:title> <jats:p>Javiera Garrido, Evelin González, Alejandro Blanco, Gonzalo Sepúlveda-Hermosilla, Matias Freire, Solange Rivas, Katherine Marcelain, Gareth I. Owen, Carolina Ibañez, Alejandro H. Corvalan, Marcelo Garrido, Rodrigo Assar, Rodrigo Lizana, Javier Cáceres-Molina, Diego Ampuero, Liliana Ramos, Paola Pérez, Osvaldo Aren, Sara Chernilo, Cristina Fernández, María Loreto Spencer, Jacqueline Flores, Giuliano Bernal, Mónica Ahumada Olea, Germán Rasse, Carolina Sánchez, Maria Galli de Amorim, Emmanuel Dias-Neto, Helano C. Freitas, Ricardo Armisen. Effects of cumulative tobacco exposure on lung cancer genomic profiles in Latin Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6440.</jats:p> </jats:sec>
2
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Clinically aggressive early‑onset pancreatic ductal adenocarcinoma with KRAS wild‑type status: A case report
(Spandidos Publications, 2026-03-06)
Maria Avendaño
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Cristopher San Martin Abello
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Fernán Gómez‑Valenzuela
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Ian Silva
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Ignacio Retamal
2
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Molecular and clinical registry of Chilean patients diagnosed with BRAF-mutated colorectal cancer
(AME Publishing Company, 2025-10)
Benjamín García-Bloj
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Tomás de Mayo Glaser
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Fernando Sigler Chávez
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Matías Muñoz-Medel
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Nicolas Cueto
1
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A germline variant of ring finger protein 43 in an early onset, treatment-resistant metastatic gastric cancer: a case report
(AME Publishing Company, 2025-08)
Benjamín García-Bloj
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Santiago Farah Celis
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Natalia Eva Orellana
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Tomás de Mayo Glasser
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Mauricio A. Sáez
1
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Comprehensive in‑silico molecular analysis of early‑onset gastric cancer identifies novel genes implicated in disease characterization and progression (Review)
(Spandidos Publications, 2025-06-17)
Fernán Gómez‑Valenzuela
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Ian Silva
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Ignacio Retamal
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Benjamín García‑Bloj
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Tomás De Mayo Glasser
1
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Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
(MDPI AG, 2025-04-03)
María José Maturana
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Oslando Padilla
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Pablo M. Santoro
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Maria Alejandra Alarcón
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Wilda Olivares
Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
1Scopus© Citations 4
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Quadruple therapies show a higher eradication rate compared to standard triple therapy for <i>Helicobacter pylori</i> infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries
(2024)
Patricio Medel‐Jara
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Diego Reyes Placencia
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Eduardo Fuentes López
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Oscar Corsi
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Gonzalo Latorre
<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Gastric cancer (GC) is one of the most lethal malignancies worldwide. <jats:italic>Helicobacter pylori</jats:italic> is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> infection who received eradication therapy and confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country‐specific variables, including prevalence of <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and <jats:italic>CYP2C19</jats:italic> polymorphisms.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>772 patients were incorporated (64.64% females; mean age of 52.93 years). The total <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT‐QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (<jats:italic>p</jats:italic>: <0.05); and 1.24 (<jats:italic>p</jats:italic>: <0.05), respectively. The antibiotic‐resistance prevalence by country, but not the prevalence of <jats:italic>CYP2C19</jats:italic> polymorphism, showed a statistically significant impact on eradication success.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Both QCT and QBT are superior to STT for <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> eradication when adjusted for country‐specific antibiotic resistance and <jats:italic>CYP2C19</jats:italic> polymorphism in a sample of individuals residing in five countries within two continents.</jats:p></jats:sec>
Scopus© Citations 3 5
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Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers
(2024)
GARRIDO MANRIQUEZ, JAVIERA NICOLE
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Yanara Bernal
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Evelin González
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Alejandro Blanco
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Gonzalo Sepúlveda-Hermosilla
Scopus© Citations 5 13
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Abstract C018: Disparities in the access to non-small cell lung cancer´s target therapies in Chile
(2023)
Solange V. Rivas
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Evelin González
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Alejandro Blanco
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Carolina Ibáñez
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Alejandro Corvalán
<jats:title>Abstract</jats:title> <jats:p>Comprehensive next-generation sequencing (NGS) panels designed to identify the tumor mutational profile are becoming the standard care to prescribe target therapies in developed countries. In non-small cell lung cancer (NSCLC), this approach significantly impacts the patient´s clinical results, measured as progression-free survival and/or overall survival, compared to conventional chemotherapies. However, as Latin American patients tend to experience more significant health disparities because of structural, sociodemographic, and psychosocial factors, in this work, our purpose is to measure the disparities in the access to NSCLC´s target therapies, specifically in Chile. DNAs and RNAs from 1643 NSCLC samples from Chile, Brazil, and Peru were sequenced to assess the mutational status in fifty-two cancer genes. After an NGS quality control, variants were called and annotated using the Variant Effect Predictor, Annovar, COSMIC, and OncoKB, to categorize somatic mutations. The following analysis focused on today’s actionable genes in NSCLC, with FDA-approved target therapies (EGFR, KRAS, ALK, MET, ERBB2, BRAF, ROS1, and RET). In this analysis, 46.5% of tumors evidenced driver mutations (764/1643); interestingly, from this subset, 86.9% showed one driver variant, 11.2% two drivers, 1.4% three drivers, and 0.5% evidenced between 4-6 driver mutations. However, 19.4% (495/1643) evidenced actionable variants. The most mutated genes and the most common actionable variants were 15.3% EGFR (37% EGFR L858R), followed by 4.9% KRAS (100% KRAS G12C), 4.5% ALK (95.4% EML4-ALK fusion), 3% MET (100% MET exon 14 skipping), and 2.3% ERBB2. Finally, 1.5% BRAF, 1% ROS1 gene fusions and 0.9% RET gene fusions. Considering the target therapies approved by Chile´s Instituto de Salud Publica until October 2021, and if all these patients were diagnosed in Chile, only 64% would receive a targeted drug. EGFR is the gene with more target therapies validated in Chile, although drugs against exon twenty insertion have not been approved yet. Chile does not account for any targeted treatment for patients with alterations in KRAS, MET, RET and ERBB2; although the FDA approved a specific drug against KRAS G12C very recently (May 28, 2021), different is the case of MET because the first inhibitor, crizotinib, was FDA approved four years ago. Interestingly, in 2021, two inhibitors against the most common MET alteration were FDA approved, but none have been approved in Chile yet. In Chile, almost all target therapies have been validated against EGFR, ALK, and BRAF; however, patients with KRAS, MET, RET, and ERBB2 cannot access specific drugs, so in these cases, the recommended therapeutic option is chemotherapy. It is important to note that the target drugs approval only ensures the availability of the drug in Chile. Still, few of the target drugs are part of financed drugs by the Chilean health system, so the question is, how could we increase the national access to existing target therapies?</jats:p> <jats:p>Citation Format: Solange V. Rivas, Evelin González, Alejandro Blanco, Carolina Ibáñez, Alejandro Corvalán, Marcelo Garrido, Gareth Owen, Katherine Marcelain, Ricardo Armisén. Disparities in the access to non-small cell lung cancer´s target therapies in Chile [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C018.</jats:p>
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