Single-Domain Antibodies as Antibody-Drug Conjugates: From Promise to Practice-A Systematic Review.

BACKGROUND: Antibody-drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due to acquired resistance and potential side effects. OBJECTIVES: This study focuses on advances in various ADC components to improve both the efficacy and safety of these agents, and includes the analysis of several novel ADC formats. This work assesses whether the unique features of VHHs-such as their small size, enhanced tissue penetration, stability, and cost-effectiveness-make them a viable alternative to conventional antibodies for ADCs and reviews their current status in ADC development. METHODS: Following PRISMA guidelines, this study focused on VHHs as components of ADCs, examining advancements and prospects from 1 January 2014 to 30 June 2024. Searches were conducted in PubMed, Cochrane Library, ScienceDirect and LILACS using specific terms related to ADCs and single-domain antibodies. Retrieved articles were rigorously evaluated, excluding duplicates and non-qualifying studies. The selected peer-reviewed articles were analyzed for quality and synthesized to highlight advancements, methods, payloads, and future directions in ADC research. RESULTS: VHHs offer significant advantages for drug conjugation over conventional antibodies due to their smaller size and structure, which enhance tissue penetration and enable access to previously inaccessible epitopes. Their superior stability, solubility, and manufacturability facilitate cost-effective production and expand the range of targetable antigens. Additionally, some VHHs can naturally cross the blood-brain barrier or be easily modified to favor their penetration, making them promising for targeting brain tumors and metastases. Although no VHH-drug conjugates (nADC or nanoADC) are currently in the clinical arena, preclinical studies have explored various conjugation methods and linkers. CONCLUSIONS: While ADCs are transforming cancer treatment, their unique mechanisms and associated toxicities challenge traditional views on bioavailability and vary with different tumor types. Severe toxicities, often linked to compound instability, off-target effects, and nonspecific blood cell interactions, highlight the need for better understanding. Conversely, the rapid distribution, tumor penetration, and clearance of VHHs could be advantageous, potentially reducing toxicity by minimizing prolonged exposure. These attributes make single-domain antibodies strong candidates for the next generation of ADCs, potentially enhancing both efficacy and safety.

Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma.

Object: Diffuse midline glioma (DMG) is a highly aggressive and lethal brain tumor predominantly affecting children and young adults. Previously known as diffuse intrinsic pontine glioma (DIPG) or grade IV brain stem glioma, DMG has recently been reclassified as "diffuse midline glioma" according to the WHO CNS5 nomenclature, expanding the DMG demographic. Limited therapeutic options result in a poor prognosis, despite advances in diagnosis and treatment. Radiotherapy has historically been the primary treatment modality to improve patient survival. Methods: This systematic literature review aims to comprehensively compile information on the diagnosis and treatment of DMG from 1 January 2012 to 31 July 2023. The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and utilized databases such as PubMed, Cochrane Library, and SciELO. Results: Currently, molecular classification of DMG plays an increasingly vital role in determining prognosis and treatment options. Emerging therapeutic avenues, including immunomodulatory agents, anti-GD2 CAR T-cell and anti-GD2 CAR-NK therapies, techniques to increase blood-brain barrier permeability, isocitrate dehydrogenase inhibitors, oncolytic and peptide vaccines, are being explored based on the tumor's molecular composition. However, more clinical trials are required to establish solid guidelines for toxicity, dosage, and efficacy. Conclusions: The identification of the H3K27 genetic mutation has led to the reclassification of certain midline tumors, expanding the DMG demographic. The field of DMG research continues to evolve, with encouraging findings that underscore the importance of highly specific and tailored therapeutic strategies to achieve therapeutic success.

Curso de superación sobre cuidados paliativos al paciente con cáncer, para médicos de familia / Updating course on palliative care for cancer patients, for General Practitioners

RESUMEN Fundamento: el cáncer es una de las principales causas de morbilidad y la primera causa de mortalidad en el mundo, entre el 30 % y 40 % de los pacientes diagnosticados se curan; el resto, inevitablemente transitará hacia etapas avanzadas y terminales, necesitará de cuidados paliativos. Objetivo: diseñar un curso de superación profesional para médicos de familia, a través del cual adquieran los conocimientos y habilidades requeridos para brindar cuidados paliativos al paciente con cáncer. Métodos: se realizó una investigación basada en el método dialéctico-materialista, con enfoque cualitativo, en el Policlínico Universitario "XX Aniversario", entre septiembre 2019-marzo 2020. Se emplearon métodos teóricos: análisis-síntesis e inducción-deducción; empíricos: análisis documental sobre contenidos relacionados con cuidados paliativos en pregrado y posgrado de la carrera de Medicina y cuestionario a los médicos para la autovaloración de sus carencias; y los matemático-estadísticos para los valores absolutos y relativos. Resultados: los profesionales muestreados autoevaluaron como regular sus conocimientos generales sobre cuidados paliativos al paciente con cáncer, la mayoría no se sintieron capacitados para brindarlos, mientras otros reconocieron insuficientes los cursos de superación, por lo que se diseñó uno compuesto por nueve temas, con sus objetivos, contenidos y formas evaluativas, el cual fue valorado por criterios de especialistas. Conclusiones: el curso de capacitación diseñado fue valorado como muy adecuado en sus aspectos: pertinencia, asequibilidad y tratamiento científico-metodológico de sus temáticas.

ABSTRACT Background: cancer is one of the main causes of morbidity and the first cause of mortality in the world, between 30% and 40% of diagnosed patients are cured; the rest will inevitably go through advanced and terminal stages, they will need palliative care. Objective: to design a professional improvement course for General Practitioners, through which they acquire the knowledge and skills required to provide palliative care to cancer patients. Methods: an investigation based on the dialectical-materialist method, with a qualitative approach, was carried out at the "XX Aniversario" University Polyclinic, from September 2019 to March 2020. Theoretical methods were used: analysis-synthesis and induction-deduction; empirical ones: documentary analysis of contents related to palliative care in undergraduate and postgraduate studies of Medicine and a questionnaire for doctors to self-assess their deficiencies; and the mathematical-statistical ones for the absolute and relative values. Results: the professionals sampled self-evaluated as average their general knowledge about palliative care to patients with cancer, most did not feel qualified to offer them, while others recognized insufficient improvement courses, so a course composed of nine topics was designed, with their objectives, contents and assessment forms, which was valued by specialist criteria. Conclusions: the designed training course was valued as very adequate in its aspects: relevance, affordability and scientific-methodological treatment of its topics.

Transformación maligna de un teratoma maduro de ovario durante la gestación / Malignant transformation of an ovarian mature teratoma during pregnancy

RESUMEN El riesgo de cáncer de ovario a lo largo de la vida de una mujer es menor de 2 %, y durante la vida reproductiva es de 0,01 %. La incidencia de cáncer de ovario durante el embarazo es de 1: 10 000 - 100 000 casos. La mayoría de las masas anexiales en la gestación son asintomáticas. El diagnóstico se realiza frecuentemente mediante un hallazgo casual en la ecografía obstétrica; se ha estimado una incidencia de 0,2 - 2 %, y de estas, 1 - 6 % son malignas. El carcinoma epidermoide desarrollado en un teratoma quístico maduro es una rara neoplasia que representa, aproximadamente, el 2 % de los tumores primarios del ovario. Se presenta una paciente con diagnóstico accidental de teratoma ovárico maduro con diferenciación de carcinoma epidermoide, durante la realización de una cesárea.

ABSTRACT The risk of ovarian cancer throughout a woman's life is less than 2%, and during reproductive life it is 0.01%. The incidence of ovarian cancer during pregnancy is 1: 10,000 - 100,000 cases. Most adnexal masses in pregnancy are asymptomatic. Diagnosis is frequently made by casual finding on obstetric ultrasound; an incidence of 0.2 - 2% has been estimated, and 1 - 6% of them are malignant. Squamous cell carcinoma developed in a mature cystic teratoma is a rare neoplasm that represents approximately 2% of primary ovarian tumors. We present a patient with an accidental diagnosis of mature ovarian teratoma with differentiation of squamous cell carcinoma, during a cesarean section.

SMILE en linfoma de células NK/T extranodal en recaída / SMILE in relapsed extranodal NK / T cell lymphoma

Introducción: El linfoma extranodal de células NK/T, tipo nasal es una variedad agresiva que se presenta con mayor frecuencia en Asia Oriental y América Latina. El régimen de tratamiento SMILE, basado en dexametasona, metotrexato, ifosfamida, L-asparaginasa y etopósido, mostró tasas de respuestas objetivas adecuadas en estudios de fase 1/2. Objetivo: presentar el primer reporte de la aplicación del protocolo SMILE en Cuba. Presentación del caso: paciente de 47 años de edad, blanca que presentó recaída temprana de linfoma extranodal de células NK/T tipo nasal en partes blandas de la pared anterior izquierda del tórax. Recibió quimioterapia SMILE por 4 ciclos y en la evaluación al final del tratamiento se comprobó que hubo una respuesta completa de la enfermedad(AU)

Introduction: Extranodal lymphoma of NK / T cells, nasal type is an aggressive variety that occurs most frequently in East Asia and Latin America. The SMILE treatment regimen, based on dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide, showed adequate objective response rates in phase 1/2 studies. Objective: to present the first report of the application of the SMILE protocol in Cuba. Case presentation : 47-year-old white patient who presented early relapse of extranodal lymphoma of nasal NK / T cells in soft parts of the left anterior wall of the thorax. He received SMILE chemotherapy for 4 cycles and the evaluation at the end of the treatment showed that there was a complete response of the disease(AU)

Linfoma de células T-natural killer tipo nasal en la piel: presentación de un caso / Nasal- type natural killer/ T-cell lymphoma involving the skin: a case report

El año 1994 marcó una línea temporal de avance y desarrollo en la investigación de cierto grupo de linfomas, caracterizados por la afectación, generalmente extranodal, en la línea media facial, la nasofaringe y la piel. La Organización Mundial de la Salud, y su más reciente revisión en el 2016, los agrupó dentro del apartado de neoplasias maduras de células T y natural killer como linfomas extraganglionares. Se presenta a una paciente, blanca, de 71 años de edad, con diagnóstico de un linfoma cutáneo de células T/natural killer tipo nasal, angiocéntrico en estadio avanzado. Se trata de un linfoma poco común, pero con curso clínico agresivo, con múltiples factores de mal pronóstico y escasa respuesta al tratamiento, que ocasionó el desenlace fatal de la paciente.