RESUMEN

Testicular cancer (TCa) is a rare malignancy affecting young men worldwide. Sociodemographic factors, especially socioeconomic level (SEL) and healthcare access, seem to impact TCa incidence and outcomes, particularly among Hispanic populations. However, limited research has explored these variables in Hispanic groups. This study aimed to investigate sociodemographic and clinical factors in Mexico and their role in health disparities among Hispanic TCa patients. We retrospectively analyzed 244 Mexican TCa cases between 2007 and 2020 of a representative cohort with diverse social backgrounds from a national reference cancer center. Logistic regression identified risk factors for fatality: non-seminoma histology, advanced stage, and lower education levels. Age showed a significant trend as a risk factor. Patient delay and healthcare distance lacked significant associations. Inadequate treatment response and chemotherapy resistance were more likely in advanced stages, while higher education positively impacted treatment response. Cox regression highlighted non-seminoma histology, below-median SEL, higher education, and advanced-stage survival rates. Survival disparities emerged based on tumor histology and patient SEL. This research underscores the importance of comprehensive approaches that integrate sociodemographic, biological, and environmental factors to address health disparities improving outcomes through personalized interventions in Hispanic individuals with TCa.

RESUMEN

Testicular germ-cell tumors (TGCT) have been widely recognized for their outstanding survival rates, commonly attributed to their high sensitivity to cisplatin-based therapies. Despite this, a subset of patients develops cisplatin resistance, for whom additional therapeutic options are unsuccessful, and ~20% of them will die from disease progression at an early age. Several efforts have been made trying to find the molecular bases of cisplatin resistance. However, this phenomenon is still not fully understood, which has limited the development of efficient biomarkers and precision medicine approaches as an alternative that could improve the clinical outcomes of these patients. With the aim of providing an integrative landscape, we review the most recent genomic and epigenomic features attributed to chemoresponse in TGCT patients, highlighting how we can seek to combat cisplatin resistance through the same mechanisms by which TGCTs are particularly hypersensitive to therapy. In this regard, we explore ongoing treatment directions for resistant TGCT and novel targets to guide future clinical trials. Through our exploration of recent findings, we conclude that epidrugs are promising treatments that could help to restore cisplatin sensitivity in resistant tumors, shedding light on potential avenues for better prognosis for the benefit of the patients.

Asunto(s)

Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Cisplatino/uso terapéutico , Epigenómica , Neoplasias Testiculares/genética , Genómica , Epigénesis Genética , Neoplasias de Células Germinales y Embrionarias/genética

RESUMEN

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Asunto(s)

Astrocitoma , Neoplasias Encefálicas , Femenino , Humanos , Masculino , Astrocitoma/patología , Biomarcadores , Neoplasias Encefálicas/patología , ADN/uso terapéutico , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Mutación , Pronóstico , Análisis de Secuencia de ADN , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/genética

RESUMEN

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.

RESUMEN

Gene mutations are strongly associated with tumor progression and are well known in cancer development. However, recently discovered epigenetic alterations have shown the potential to greatly influence tumoral response to therapy regimens. Such epigenetic alterations have proven to be dynamic, and thus could be restored. Due to their reversible nature, the promising opportunity to improve chemotherapy response using epigenetic therapy has arisen. Beyond helping to understand the biology of the disease, the use of modern clinical epigenetics is being incorporated into the management of the cancer patient. Potential epidrug candidates can be found through a process known as drug repositioning or repurposing, a promising strategy for the discovery of novel potential targets in already approved drugs. At present, novel epidrug candidates have been identified in preclinical studies and some others are currently being tested in clinical trials, ready to be repositioned. This epidrug repurposing could circumvent the classic paradigm where the main focus is the development of agents with one indication only, while giving patients lower cost therapies and a novel precision medical approach to optimize treatment efficacy and reduce toxicity. This review focuses on the main approved epidrugs, and their druggable targets, that are currently being used in cancer therapy. Also, we highlight the importance of epidrug repurposing by the rediscovery of known chemical entities that may enhance epigenetic therapy in cancer, contributing to the development of precision medicine in oncology.