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Drug repositioning is a alternative strategy to discover and develop anticancer drugs based on identification of new mechanisms of actions and indications for existing compounds. Ivermectin belongs to the avermectin group of compounds, a series of 16-membered macrocyclic lactone moieties discovered in 1967 and FDA-approved for human use since 1987. Ivermectin has since been used by millions of people worldwide, and have demonstrated a wide margin of clinical safety. Here we summarize the in vitro and in vivo evidence demonstrating ivermectin\'s potential as a multitargeting anticancer drug that exerts antitumor effects against different tumor types. Notably, the in vitro and in vivo antitumor activities of ivermectin are achieved at concentrations that can be clinically achieved based on human pharmacokinetic studies done in the clinical studies. Moreover, repurposed ivermectin safety has been well established recently in clinical studies against COVID-19. Consequently, we believe that ivermectin is an excellent potential candidate drug that can be repurposed for cancer and deserves rigorous evaluation against a variety of cancers in well-designed clinical trials.

Background Novel prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) are required in the era of Rituximab. Objective The objective of the study was to study the prognostic impact of exon-16 enhancer-of-zeste homolog-2 (EZH2) mutations in patients with DLBCL. Methods In a cohort of patients with DLBCL treated between 2015 and 2017, we analyzed the presence of EZH2 mutations and their association with clinical response (CR), relapse, progression-free survival (PFS), and overall survival (OS). Results A total of 198 patients were included; of them, 30 (15.2%) had mutations at codon 641, in exon 16 of EZH2. Response was achieved in 151 patients (76.3%), and 43 (21.7%) relapsed or progressed during follow-up. EZH2 mutations were associated with relapse/progression (risk ratio [RR] 1.18; 95% confidence interval [CI] 0.98-1.42; p = 0.031), while a trend for not achieving a complete response was observed (RR: 0.876; 95%CI 0.74-1.038; p = 0.071). Of note, Tyr641His and Tyr641Ser EZH2 mutations were associated with shorter PFS (hazard ratio 3.234; 95% CI 1.149-9.1; p = 0.026). Conclusion The presence of EZH2 mutations was negatively associated with relapse/progression and showed a trend for lack of complete response. Further studies are needed to define better the prognostic significance of these mutations in Mexican-Mestizo DLBCL patients.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin lymphoma worldwide. The current standard of care is chemoimmunotherapy with an R-CHOP regimen. We aim to review the role of this regimen after two decades of being the standard of care. Methods: A comprehensive literature review of DLBCL, including the epidemiology, trials defining R-CHOP as the standard of care, as well as dose intensification and dose reduction schemes. Additionally, we briefly review the development of rituximab biosimilars and the addition of targeted drugs to R-CHOP in clinical trials. Discussion: R-CHOP cures approximately 70% of DLBCL patients. Dose-dense regimens do not show a benefit in response and increase toxicity. Dose reduction, particularly in elderly patients or with comorbidities, may be a treatment option. DLBCL constitutes a group of diseases that activate different biological pathways. Matching specific treatments to a defined genetic alteration is under development. Rituximab biosimilars have become available to a broader population, particularly in developing countries, where access to treatment is limited because of economic resources. Conclusion: DLBCL landscape is heterogeneous. R-CHOP immunochemotherapy has been a standard of care for two decades and cures approximately 70% of cases. Molecular characterization of patients is evolving and may have critical therapeutic implications.

Enrique Pérez-Cárdenas,1 Lucía Taja-Chayeb,1 Catalina Trejo-Becerril,1 José Chanona-Vilchis,2 Alma Chávez-Blanco,1 Guadalupe Domínguez-Gómez,1 Elizabeth Langley,1 Alejandro García-Carrancá,3,4 Alfonso Dueñas-González3,4 1Division of Basic Research, Instituto Nacional de Cancerología, Mexico City, Mexico; 2Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico; 3Unit of Biomedical Research on Cancer, Biomedical Research Institute, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico; 4Unit of Biomedical Research on Cancer, Instituto Nacional de Cancerologia, Mexico City, Mexico Introduction: Metastasis involves the accumulation of genetic and epigenetic alterations leading to activation of prometastatic genes and inactivation of antimetastatic genes. Among epigenetic alterations, DNA hypermethylation and histone hypoacetylation are the focus of intense translational research because their pharmacological inhibition has been shown to produce antineoplastic activity in a variety of experimental models. Aims: This study aimed to evaluate the antimetastatic effect of the DNA-methylation inhibitor, hydralazine, and the histone deacetylase inhibitor, valproic acid. Methods: NIH 3T3-Ras murine cells were treated with hydralazine and valproic acid to evaluate their effects upon cell proliferation, cell motility, chemotaxis, gelatinase activity, and gene expression. Lung metastases were developed by intravenous injection of NIH 3T3-Ras cells in BALB/c nu/nu mice and then treated with the drug combination. Results: Treatment induced a growth-inhibitory effect on NIH 3T3-Ras cells, showed a trend toward increased gelatinase activity of MMP2 and MMP9, and inhibited chemotaxis and cell motility. The combination led to a strong antimetastatic effect in lungs of nude mice. Conclusion: Hydralazine and valproic acid, two repositioned drugs as epigenetic agents, exhibit antimetastatic effects in vitro and in vivo and hold potential for cancer treatment. Keywords: hydralazine, valproic acid, epigenetics, metastasis, ras

Cervical cancer is the fourth most common cancer in women with 85% of the mortality burden occurring in less-developed regions of the world. The Cervix Cancer Research Network (CCRN) was founded by the Gynecologic Cancer InterGroup (GCIG) with a mission to improve outcomes in cervix cancer by increasing access to high-quality clinical trials worldwide, with particular attention to less-developed, underrepresented sites. The CCRN held its second international educational symposium in Mexico City with ninety participants from fifteen Latin America countries in January 2017. The purpose of this symposium was to advance knowledge in cervix cancer therapy, promote recruitment to CCRN clinical trials, and to identify relevant future CCRN clinical trial concepts that could improve global care standards for women with cervical cancer., Highlights • Cervix cancer is the fourth most common cancer in women worldwide with up to an 18-fold disparity in mortality rates. • The Cervix Cancer Research Network (CCRN) aims to increase access to clinical trials in order to improve outcomes for women. • The 2nd CCRN international symposium was held in Mexico City including 90 participants from 15 Latin American countries. • CCRN clinical trials were discussed, including new trials proposed of hypofractionation and HPV targeted therapy.

Algunas de las variables que tratan de representar el medio ambiente son de difícil medida, por lo que suelen estimarse en función de otras mediante modelos, propa- gando el error de los datos de origen. El presente artículo es una recopilación bibliográfica de los aspectos más importantes a considerar al analizar la propagación del error en modelos con datos de entradas espaciales y salidas discretas sobre vari- ables medioambientales. Debido a que estos modelos suelen tener datos de entrada en forma de variables discretas, también se aborda la influencia de sus fuentes de error en su propagación por los modelos cartográficos. Las fuentes de error más importantes en los datos de entrada de este tipo son la adecuada determinación de las clases, la identificación de la categoría —error temático y conceptual—, la localización de sus bordes —precisión y exactitud cartográfica— y la escala, considerándose como variables en los análisis de propagación de errores. Una vez conocida la fuente del error, posteriormente se analizan diferentes tra- bajos de análisis de sensibilidad de algunos modelos que pueden servir como refe- rencia para el estudio de otras variables medioambientales discretas. Monte Carlo se muestra como un método idóneo para el análisis de propagación de errores para variables discretas, aunque no se ha encontrado bibliografía que compare diferentes métodos para un mismo juego de datos ni modelo. Se analizan ciertas particularida- des de cada modelo de datos —raster y vectorial— y su influencia en el resultado.