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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
;
Evelin González
;
Alejandro Blanco
;
Gonzalo Sepúlveda-Hermosilla
;
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>
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A snapshot of cancer in Chile II: an update on research, strategies and analytical frameworks for equity, innovation and national development
(Springer Science and Business Media LLC, 2024-12-18)
Cristóbal Vacarezza
;
Julieta Araneda
;
Pamela Gonzalez
;
Oscar Arteaga
;
Katherine Marcelain
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Introduction</jats:title> <jats:p>Chile has achieved developed nation status and boasts a life expectancy of 81 + years; however, the healthcare and research systems are unprepared for the social and economic burden of cancer. One decade ago, the authors put forward a comprehensive analysis of cancer infrastructure, together with a series of suggestions on research orientated political policy.</jats:p> </jats:sec><jats:sec> <jats:title>Objectives</jats:title> <jats:p>Provide an update and comment on policy, infrastructure, gender equality, stakeholder participation and new challenges in national oncology. Assess the funding and distribution of cancer investigation. Present actions for the development of oncology research, innovation and patient care.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Triangulating objective system metrics of economic, epidemiological, private and public sector resources together with policy analysis, we assessed cancer burden, infrastructure, and investigation. We analyzed governmental and private-sector cancer databases, complemented by interviews with cancer stakeholders.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Governmental policy and patient advocacy have led to the recognition of cancer burden, a cancer law, and a national cancer plan. Cancer has become the leading cause of death in Chile (59,876 cases and 31,440 cancer deaths in 2022), yet only 0.36% gross domestic product (GDP) is directed to research and development. Inequalities in treatment regimens persist. Prevention policy has lowered tobacco consumption, sugar intake via soft drinks and offered a high coverage of HPV vaccines. A high-quality cancer research community is expanding, and internationally sponsored clinical oncology trials are increasing.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The cancer law has facilitated advancement in policy. Prevention policies have impacted tobacco and sugar intake, while gender equality and care inequality have entered the public forum. Cancer research is stagnated by the lack of investment. Implementation of a cancer registry and biobanking, reinforcement of prevention strategies, development of human resources, promotion of clinical trial infrastructure and investment in new technologies must be placed as a priority to permit advancements in innovation and equitable cancer care.</jats:p> </jats:sec>
8
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Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors
(2020)
Pablo Lara
;
Sujey Palma-Florez
;
Edison Salas-Huenuleo
;
Iva Polakovicova
;
Simón Guerrero
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.</jats:p> </jats:sec>
11 1Scopus© Citations 88

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