RESUMO
Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Inibidores de Proteínas Quinases/farmacologia , MutaçãoRESUMO
Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) "What is the current knowledge about polyploidy in tumors?"; (ii) "What are the applications of computational studies for the understanding of cancer polyploidy?"; and (iii) "How do PGCCs contribute to tumorigenesis?"
Assuntos
Células Gigantes , Recidiva Local de Neoplasia , Humanos , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , Células Gigantes/metabolismo , Células Gigantes/patologia , Poliploidia , Biologia ComputacionalRESUMO
Introdução: A diabetes tipo 2 (DM2) é uma desordem metabólica ocasionada pela disfunção das células beta pancreáticas que interferem na produção de insulina e/ou pela resistência dos órgãos alvos a esse hormônio. Níveis elevados de radicais livres em conjunto com o declínio das defesas antioxidantes presente na DM2 podem ocasionar danos a organelas celulares, promovendo complicações da doença. As glutationas S- transferases (GST) são as principais enzimas antioxidantes que participam da defesa celular contra o estresse oxidativo. Os polimorfismos nos genes que codificam essas enzimas podem acarretar o surgimento de complicações oftalmológicas em diabéticos. Este trabalho avaliou a influência dos polimorfismos nos genes GST no desenvolvimento de doenças como a catarata e o glaucoma em pacientes com DM2 na Grande Vitória (ES). Metodologia: Os polimorfismos dos genes GSTM1 e GSTT1 foram investigados através da técnica de PCR multiplex. Para o gene GSTP1 utilizou-se a técnica PCR- RFLP. A análise estatística foi realizada através do teste exato de Fisher ou do teste do qui-quadrado com P-valor < 0.05. Resultados: Não foi encontrada relação entre os polimorfismos nos genes GSTM1, GSTT1 e GSTP1 e o surgimento de doenças como glaucoma e catarata em pacientes com DM2. Conclusão: Nossos dados sugerem que os polimorfismos nulos nos genes GSTM1 e GSTT1 e o polimorfismo Ile105Val no gene GSTP1 não estão associados com a suscetibilidade individual para o desenvolvimento de complicações oftalmológicas em pacientes com DM2. (AU)
Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by beta cell dysfunction that interferes with insulin production and/or by the resistance of target organs to this hormone. An increase in free radicals together with a decline in antioxidant defenses, present in T2DM, can damage cellular organelles and promote the occurrence of disease complications. Glutathione S-transferases (GSTs) are the main antioxidant enzymes involved in cellular defense against oxidative stress, and polymorphisms in genes encoding GSTs can lead to ophthalmic complications in persons with diabetes. In this study, we evaluated the influence of GST polymorphisms on the development of diseases such as cataract and glaucoma in patients with T2DM in Grande Vitória, Espírito Santo, Brazil. Methods: GSTM1 and GSTT1 polymorphisms were investigated using a multiplex PCR technique. PCR-RFLP was used for the GSTP1 gene. Statistical analysis was performed with Fisher's exact test or the chi-square test, with P-value <0.05. Results: There was no relationship between GSTM1, GSTT1, or GSTP1 polymorphisms and the occurrence of diseases such as glaucoma and cataract in patients with T2DM. Conclusion: Our data suggest that the GSTM1 and GSTT1 null polymorphisms and the ile105Val polymorphism in the GSTP1 gene are not associated with individual susceptibility to the development of ophthalmic complications in persons with T2DM. (AU)
