Current and Emerging Treatment Paradigms in Colorectal Cancer: Integrating Hallmarks of Cancer.

The treatment of unresectable metastatic colorectal cancer has evolved over the last two decades, as knowledge of cancer biology has broadened and new targets have emerged. 'The Hallmarks of Cancer' illustrate the crucial capabilities acquired by cells to become malignant and represent the evolution of knowledge of tumor biology. This review integrates these novel targets and therapies into selected hallmarks: sustaining proliferative signaling, inducing vasculature, avoiding immune destruction, genome instability and mutation, reprogramming cellular metabolism, and resisting cell death. The different strategies and combinations under study are based on treatments with anti-EGFR, anti-VEGF, and anti-HER2 agents, KRAS G12C inhibitors, BRAF and MEK inhibitors, and immune checkpoint inhibitors. However, new approaches are emerging, including vaccines, WEE1 inhibitors, and PARP inhibitors, among others. The further deciphering of cancer biology will unravel new targets, develop novel therapies, and improve patients' outcomes.

Targeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver.

Kirsten rat sarcoma virus oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancer. In colorectal cancer (CRC), KRAS mutations are present in more than 50% of cases, and the KRAS glycine-to-cysteine mutation at codon 12 (KRAS G12C) occurs in up to 4% of patients. This mutation is associated with short responses to standard chemotherapy and worse overall survival compared to non-G12C mutations. In recent years, several KRAS G12C inhibitors have demonstrated clinical activity, although all patients eventually progressed. The identification of negative feedback through the EGFR receptor has led to the development of KRAS inhibitors plus an anti-EGFR combination, thus boosting antitumor activity. Currently, several KRAS G12C inhibitors are under development, and results from phase I and phase II clinical trials are promising. Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation. Nonetheless, most of these patients will eventually relapse. In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance.

Cetuximab as a Key Partner in Personalized Targeted Therapy for Metastatic Colorectal Cancer.

Cetuximab, a chimeric IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has revolutionized personalized treatment of metastatic colorectal cancer (mCRC) patients. This review highlights the mechanism of action, characteristics, and optimal indications for cetuximab in mCRC. Cetuximab has emerged as a pivotal partner for novel therapies in specific molecular subgroups, including BRAF V600E, KRAS G12C, and HER2-altered mCRC. Combining cetuximab with immunotherapy and other targeted agents further expands the therapeutic landscape, offering renewed hope for mCRC patients who face the development of resistance to conventional therapies. Ongoing clinical trials have continued to uncover innovative cetuximab-based treatment strategies, promising a brighter future for mCRC patients. This review provides a comprehensive overview of cetuximab's role and its evolving importance in personalized targeted therapy of mCRC patients, offering valuable insights into the evolving landscape of colorectal cancer treatment.

Epidermal growth factor receptor antagonists in colorectal cancer: emerging strategies for precision therapy.

INTRODUCTION: The global prevalence of colorectal cancer highlights the need to enhance treatment strategies for improved patient outcomes. The pivotal role of epidermal growth factor receptor (EGFR) signaling in regulating cellular processes for this disease pinpoints its value as a therapeutic target, despite the emergence of resistance mechanisms over time. AREAS COVERED: This review discusses the clinical evidence supporting the use of EGFR inhibitors in molecularly-selected patients based on molecular characteristics (notably BRAF V600E and KRAS G12C) including combination approaches targeting different points in in the signaling pathway, as well as strategies such as EGFR inhibitor rechallenge. The role of HER2 inhibitors and emerging approaches such as bispecific antibodies are also reviewed. EXPERT OPINION: Recently, inhibitors targeting the KRAS G12C variant have emerged, albeit with modest monotherapy activity compared to other tumor types, emphasizing the influence of histologic origins on the EGFR signaling pathway. Integration of EGFR inhibitors into precision medicine has facilitated tailored therapies addressing resistance mechanisms. Patient selection for EGFR inhibitor rechallenge guided by ctDNA findings is crucial, with ongoing investigations exploring novel combinations to enhance EGFR blockade, highlighting the transformative potential of precision medicine in shaping the future of mCRC treatment toward personalized and targeted approaches.

Unravelling the Complexity of Colorectal Cancer: Heterogeneity, Clonal Evolution, and Clinical Implications.

Colorectal cancer (CRC) is a global health concern and a leading cause of death worldwide. The disease's course and response to treatment are significantly influenced by its heterogeneity, both within a single lesion and between primary and metastatic sites. Biomarkers, such as mutations in KRAS, NRAS, and BRAF, provide valuable guidance for treatment decisions in patients with metastatic CRC. While high concordance exists between mutational status in primary and metastatic lesions, some heterogeneity may be present. Circulating tumor DNA (ctDNA) analysis has proven invaluable in identifying genetic heterogeneity and predicting prognosis in RAS-mutated metastatic CRC patients. Tumor heterogeneity can arise from genetic and non-genetic factors, affecting tumor development and response to therapy. To comprehend and address clonal evolution and intratumoral heterogeneity, comprehensive genomic studies employing techniques such as next-generation sequencing and computational analysis are essential. Liquid biopsy, notably through analysis of ctDNA, enables real-time clonal evolution and treatment response monitoring. However, challenges remain in standardizing procedures and accurately characterizing tumor subpopulations. Various models elucidate the origin of CRC heterogeneity, highlighting the intricate molecular pathways involved. This review focuses on intrapatient cancer heterogeneity and genetic clonal evolution in metastatic CRC, with an emphasis on clinical applications.

The impact of clinical and translational research on the quality of life during the metastatic colorectal cancer patient journey.

The journey of metastatic colorectal cancer patients is complex and challenging, requiring coordination and collaboration between multiple healthcare providers. Understanding patients' needs, fears, feelings, concerns, and behaviors is essential for providing individualized patient-centered care. In recent years, mCRC patients have experienced improvements in clinical outcomes, from 16 months of overall survival to 32 months, thanks to research. However, there is still room for improvement, and integrating clinical and translational research into routine practice can help patients benefit from treatments and techniques that would not be an option. In the Journey of mCRC patients, living well with cancer and quality of life becomes a priority given the outcomes of the disease. Patient reported outcomes (PRO) and Patient Reported Outcome Measures (PROMs) are becoming therefore new estimands in Oncology. Patient advocates represent important figures in this process by prioritizing issues and research questions; evaluating research designs and the performance of the research; the analysis and interpretation of data; and how results are disseminated. Multidisciplinary Tumor Boards and shared decision-making is essential for designing treatment strategies for individual patients. Quality of Life is often prioritized only when it comes to refractory advanced disease and end-of-life care, but it has to be integrated from the beginning, as the emotional impact of diagnosis leads to a vulnerable situation where patients' needs and preferences can be easily overseen. First-line treatment will be chosen among more treatment options than subsequent lines, with longer progression-free survival and a bigger impact on the outcomes. Practicing patient-centered care and optimizing first-line treatment for colorectal cancer patients requires a comprehensive understanding of patient experience and treatment outcomes, which can guide clinical practice and inform regulatory decisions for the benefit of patients.

Accidentes cortopunzantes en personal de salud / Sharp-edged accidents in health personnel

Introducción. Un accidente biológico es una exposición del personal de salud a fluidos potencialmente infecciosos. Cuando ocurren estos accidentes, siempre deben ser considerados de alta prioridad para la protección del personal de salud. La población más afectada es el personal de enfermería, personal de limpieza y médicos. Objetivos. Describir la frecuencia de accidentes con objetos cortopunzantes en el personal de salud en un hospital de tercer nivel, reportes a las autoridades correspondientes, vacunación para hepatitis B y participación en capacitaciones en bioseguridad. Materiales y métodos. Se realizó un estudio observacional, descriptivo y transversal a través de una encuesta en línea por Google Forms™ al personal sanitario de un hospital de tercer nivel. Resultados. Se obtuvieron 26 respuestas, de las cuales el 92,3% era personal médico y el 7,7%, licenciados o técnicos de enfermería. El 57,7% de las personas eran varones. El 88,5% informó estar inmunizado contra la hepatitis B. Se reportaron 6 de cada 10 accidentes. Conclusión. La mayoría de los resultados coinciden con la bibliografía, como el número de accidentes notificados, porcentaje de vacunación contra la hepatitis B y los motivos por los que no fueron notificados. Promover la capacitación en bioseguridad es el primer paso para garantizar la protección del personal de salud, pues al prevenir estos eventos se reduce la exposición y el riesgo de transmisión de enfermedades. Palabras Clave: personal de salud; accidentes e incidentes biológicos; contención de riesgos biológicos; capacitación del personal

Introduction. A biological accident is an exposure of health personnel to potentially infectious fluids. When these accidents occur, they should always be considered a high priority for the protection of health personnel. The most affected population is the nursing staff, cleaning staff and doctors. Objectives.Describe the frequency of accidents with sharp objects in health personnel in a tertiary hospital, reports to relevant authorities, vaccination for hepatitis B and participation in biosafety training. Materials and methods.An observational, descriptive and cross-sectional study is carried out through an online survey by Google Forms™ to health professionals. Results. Were obtained 26 responses, which 92,3% belonged to medical personnel, 7,7% were graduates or nursing technicians. The 57,7% of the people were male. The 88,5% reported having immunization against Hepatitis B. 6 out of 10 accidents were reported. Conclusion. Most of the results equal the bibliography, like the number of accidents reported, percentage of vaccination against Hepatitis B, and the motives they weren't reported. Promoting biosafety training is the first step to guarantee the protection of health personnel, because by preventing these events, exposure and risk of disease transmission is reduced. Key words: health personnel; biological accidents and events; containment of biohazards; in-service training

Vacunación contra el SARS-CoV-2 en el personal de salud / Vaccination against SARS-CoV-2 in health personnel

Introducción: El virus Sars-cov2 es el causante de una enfermedad respiratoria, cuyo grado de severidad es variable, de formas sintomáticas leves a graves. Debido a que no se ha encontrado un tratamiento eficaz para hacerle frente a esta patología, se ha puesto el foco en la prevención mediante vacunas. Una población objetivo de la primera y segunda fase de vacunación a nivel país, fue el personal de salud, por lo que se realiza una encuesta para determinar qué tipo de patologías de base presentan, rango etario predominante, si presentaron algún efecto adverso, y cuántas dosis de inmunización recibieron. Objetivos: Describir el porcentaje de vacunación contra Sars-cov2 en el personal de salud, las enfermedades de base, efectos adversos presentados y describir los motivos por el que se evita la vacunación. Materiales y métodos: Se realizó un estudio descriptivo, observacional y transversal mediante una encuesta en línea (Google Forms). En el cuestionario se registraron las siguientes variables: sexo, edad, profesión dentro del área de salud, departamento de residencia, enfermedad de base, dosis principales y de refuerzo recibidas, efectos adversos presentados, necesidad de atención médica posterior y razones por las que no se han aplicado todas las dosis. Resultados: La mayoría de los encuestados fueron parte del personal médico (85.4%), en su mayoría se encontraban entre los 20-29 años y los 40-49 años. El 48.6% no presenta patologías de base. El 96.3% de la población recibió 2 dosis de la vacuna para Sars-cov2. El 46.3% recibió 2 dosis de refuerzo. Discusión: La predisposición a completar el esquema fue más baja de lo esperado, siendo menor de la mitad. La predisposición para recibir la vacuna contra el COVID-19, en la población general fue de 52,02%. Cabe recalcar que el éxito de un programa de vacunación depende de la proporción de la población que desee vacunarse. Conclusión: La vacunación es un medio de prevención por lo que su promoción es un paso importante para evitar la enfermedad grave. Es necesario realizar una buena educación a toda la población sobre la eficacia, las dosis necesarias para obtener inmunidad, los efectos adversos y los motivos que deben retrasar la colocación de las dosis, porque, como se menciona anteriormente, el éxito de un programa de vacunación depende de la proporción de la población que desee vacunarse.

Introduction: The Sars-cov2 virus is the cause of a respiratory disease, whose degree of severity is variable, from mild to severe symptomatic forms. Since no effective treatment has been found to deal with this pathology, the focus has been on prevention through vaccination. A target population for the first and second phase of vaccination at the country level was health personnel. So a online survey is performed to determine what type of underlying pathologies they present, the age range predominance, the side effects displayed and how many doses they received. Objectives: Describe the percentage of vaccination against Sars-cov2 in health personnel, the underlying diseases, adverse effects and, to describe the reasons why vaccination is avoided. Materials and methods: A descriptive, observational and cross-sectional study is carried out using an online survey (Google Forms). The following variables were recorded in the questionnaire: sex, age, profession within the health area, department of residence, underlying disease, main and booster doses received, adverse effects presented, need for subsequent medical attention and reasons why they did not have been applied all the doses. Results: Most of the respondents were part of the medical staff (85.4%), the majority were between 20-29 years and 40-49 years. The 48.6% do not present basic pathologies. The 96.3% of the population received 2 doses of the Sars-cov2 vaccine. 46.3% received 2 booster doses. Discussion: The predisposition to complete the scheme was lower than expected, being less than a half. The predisposition to receive the COVID-19 vaccine in the general population was 52.02%. It should be emphasized that the success of a vaccination program depends on the proportion of the population that wishes to be vaccinated. Conclusion: Vaccination is a way of prevention, so its promotion is an important step to avoid a serious disease. It is necessary to give a good education to the entire population about the efficacy, the necessary doses to obtain immunity, the adverse effects and the reasons that should delay the doses, because, as mentioned above, the success of a vaccination program depends on the proportion of the population that wants to be vaccinated.

Proyecto industrial planta procesadora de cartón corrugado

Los productos a ser fabricados son cajas y bandejas fabricadas a partir de cartón corrugado y son elaboradas a partir de planchas de cartón ondulado cuyo formato es determinado en las unidades de corte y ranurado longitudinal