MEK inhibitor sensitivity in BRAF fusion-driven prostate cancer

Purpose The identification of subpopulations harboring druggable targets has become a major step forward in the subclassification of solid tumors into small groups suitable for specific therapies. BRAF fusions represent a paradigm of uncommon and targetable oncogenic events and have been widely correlated to the development of specific malignancies. However, they are only present in a limited frequency across most common tumor types. At this regard, we performed a genomic screening aimed to identifying rare variants associated to advanced prostate cancer development. Methods Tumoral tissue genomic screening of 41 patients developing advanced prostate cancer was performed at our center as part of the GETHI XX study. The project, sponsored by the Spanish Collaborative Group in Rare Cancers (GETHI), aims to analyze the molecular background of rare tumors and to discover unfrequent molecular variants in common tumors. Results Here we present the clinical outcome and an in-deep molecular analysis performed in a case harboring a SND1-BRAF fusion gene. The identification of such rearrangement in a patient refractory to standard therapies led to the administration of trametinib (MEK inhibitor). Despite unsensitive to standard therapies, the patient achieved a dramatic response to trametinib. A comprehensive study of the tumor demonstrated this event to be a trunk alteration with higher expression of MEK in areas of tumor invasion. Conclusions Our study describes the patient-driven discovery of the first BRAF fusion-driven prostate cancer effectively treated with trametinib. Consequently, MAPK pathway activation could define a new subtype of prostate cancer susceptible to a tailored management. (AU)

MEK inhibitor sensitivity in BRAF fusion-driven prostate cancer.

PURPOSE: The identification of subpopulations harboring druggable targets has become a major step forward in the subclassification of solid tumors into small groups suitable for specific therapies. BRAF fusions represent a paradigm of uncommon and targetable oncogenic events and have been widely correlated to the development of specific malignancies. However, they are only present in a limited frequency across most common tumor types. At this regard, we performed a genomic screening aimed to identifying rare variants associated to advanced prostate cancer development. METHODS: Tumoral tissue genomic screening of 41 patients developing advanced prostate cancer was performed at our center as part of the GETHI XX study. The project, sponsored by the Spanish Collaborative Group in Rare Cancers (GETHI), aims to analyze the molecular background of rare tumors and to discover unfrequent molecular variants in common tumors. RESULTS: Here we present the clinical outcome and an in-deep molecular analysis performed in a case harboring a SND1-BRAF fusion gene. The identification of such rearrangement in a patient refractory to standard therapies led to the administration of trametinib (MEK inhibitor). Despite unsensitive to standard therapies, the patient achieved a dramatic response to trametinib. A comprehensive study of the tumor demonstrated this event to be a trunk alteration with higher expression of MEK in areas of tumor invasion. CONCLUSIONS: Our study describes the patient-driven discovery of the first BRAF fusion-driven prostate cancer effectively treated with trametinib. Consequently, MAPK pathway activation could define a new subtype of prostate cancer susceptible to a tailored management.

Disfagia en una paciente con carcinoma renal metastásico / Dysphagia in a patient with metastatic renal cancer

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[Immunity against hepatitis A virus in patients with chronic hepatitis C]. / Inmunidad frente al virus de la hepatitis A en los pacientes con infección crónica por el virus de la hepatitis C.

BACKGROUND AND OBJECTIVE: Because of high fatality rate associated with acute infection by hepatitis A virus (HAV) in chronic hepatitis C patients, it is of interest to know the prevalence of immunization against HAV in these patients. PATIENTS AND METHOD: Immunoglobulin G (IgG) IgG HAV antibodies (IgG anti-HAV) were determined in 313 hepatitis C virus antibodies (anti-HCV) positive patients and in 313 anti-HCV negative subjects (control group). Several epidemiological factors were recorded (age, sex, rural vs urban precedence, tattoos, parenteral drugs use, alcohol consumption and surgery). RESULTS: The prevalence of IgG anti-HAV was identical in both groups: 81.2%. However, in those younger than 41 years, this prevalence was greater in those anti-HCV positive than in the control group. Parenteral drugs use and tattoos were more frequent in the first group. The presence of IgG anti-HAV was associated with age and the rural origin in both groups. CONCLUSIONS: The prevalence of IgG anti-HAV increases with age, and is more frequent in individuals with rural origin. It was also greater in young anti-HCV positive patients, when compared with controls of the same age. This finding can be due to the poor standards of hygiene probably associated with some practices more common in this population, such as parenteral drugs use, tattoos and others.

Inmunidad frente al virus de la hepatitis A en los pacientes con infección crónica por el virus de la hepatitis C / Immunity against hepatitis A virus in patients with chronic hepatitis C

FUNDAMENTO Y OBJETIVO: Debido a la mayor morbimortalidad de la hepatitis aguda por el virus dela hepatitis A (VHA) cuando ocurre en pacientes con infección crónica por el virus de la hepatitisC (VHC), interesa conocer la prevalencia de inmunización frente al VHA en estos pacientes.PACIENTES Y MÉTODO: Se determinaron los anticuerpos de tipo inmunoglobulina G (IgG) frente alVHA (IgG anti-VHA) en 313 pacientes con infección crónica por el VHC (anti-VHC) y en 313 individuosanti-VHC negativo.RESULTADOS: La prevalencia de IgG anti-VHA encontrada fue idéntica en ambos grupos: un81,2%. Sin embargo, entre los menores de 41 años esta prevalencia era mayor en los anti-VHCpositivo que en los individuos del grupo control. La adicción a drogas por vía parenteral y lostatuajes fueron más frecuentes en el primer grupo. La presencia de IgG anti-VHA se asoció conla edad y con la procedencia del medio rural en ambos grupos.CONCLUSIONES: La prevalencia de IgG anti-VHA aumenta con la edad y es más elevada entre losindividuos de procedencia rural. También podría ser mayor entre los pacientes jóvenes anti-VHC positivo, en comparación con los controles de edad similar. Este hallazgo puede deberse alas peores condiciones higiénicas probablemente asociadas con ciertas prácticas más comunesentre estos individuos, como la adicción a drogas por vía parenteral y los tatuajes

BACKGROUND AND OBJECTIVE: Because of high fatality rate associated with acute infection by hepatitisA virus (HAV) in chronic hepatitis C patients, it is of interest to know the prevalence of immunizationagainst HAV in these patients.PATIENTS AND METHOD: Immunoglobulin G (IgG) IgG HAV antibodies (IgG anti-HAV) were determinedin 313 hepatitis C virus antibodies (anti-HCV) positive patients and in 313 anti-HCV negativesubjects (control group). Several epidemiological factors were recorded (age, sex, rural vsurban precedence, tattoos, parenteral drugs use, alcohol consumption and surgery).RESULTS: The prevalence of IgG anti-HAV was identical in both groups: 81.2%. However, in thoseyounger than 41 years, this prevalence was greater in those anti-HCV positive than in thecontrol group. Parenteral drugs use and tattoos were more frequent in the first group. The presenceof IgG anti-HAV was associated with age and the rural origin in both groups.CONCLUSIONS: The prevalence of IgG anti-HAV increases with age, and is more frequent in individualswith rural origin. It was also greater in young anti-HCV positive patients, when comparedwith controls of the same age. This finding can be due to the poor standards of hygiene probablyassociated with some practices more common in this population, such as parenteraldrugs use, tattoos and others