Combination therapies with HSP90 inhibitors against colorectal cancer

Oncogene stability and homeostasis mediated by the HSP90 chaperone is a crucial protection trait of cancer cells. Therefore, HSP90 represents an attractive therapeutic target for many cancers, including colorectal cancer. Although monotherapy has limited clinical efficacy, preclinical and early-phase clinical studies indicate improved antitumor activity when HSP90 inhibitors are combined with chemotherapies or targeted agents. This may be further improved with a biomarker-guided approach based on oncogenic HSP90 clients, or stratification based on the consensus molecular subtypes of colorectal cancer, suggesting a synergistic activity with 5-fluorouracil in preclinical models of the chemorefractory mesenchymal subtype. Furthermore, HSP90 inhibition may activate mechanisms to turn non-immunogenic tumors hot and improve their recognition by the immune system, suggesting synergy with immune checkpoint blockade.     

Age-related Epstein-Barr virus-positive cutaneous ulcer arising after a self-limited subcutaneous abscess: a case report

ABSTRACT: INTRODUCTION: Epstein-Barr virus-positive mucocutaneous ulcer is a newly recognized clinicopathologic entity in the spectrum of Epstein-Barr virus-positive lymphoproliferative disorders. This entity is characterized by a self-limited, indolent course. CASE PRESENTATION: We report the case of a 74-year-old, type 2 diabetic man who presented with an ulceroinfiltrative skin lesion on the left side of his neck. Histological examination showed that the lesion consisted of large atypical cells, some with Hodgkin-Reed-Sternberg-like morphology, in the midst of reactive lymphocytes, plasma cells, eosinophils and histiocytes. The atypical cells were partially positive for CD45, CD20, CD79a, CD30, B-cell lymphoma 2 and latent membrane protein 1 (CS.1-4), and negative for CD15, B-cell lymphoma 6 and CD10. In situ hybridization for Epstein-Barr virus-encoded ribonucleic acid was positive. Two years before, the patient had been diagnosed with a self-limited subcutaneous abscess in the same anatomic area that healed after antibiotic therapy. CONCLUSION: Older patients with positive Epstein-Barr virus serology may develop B-cell lymphoproliferations due to age-related immune suppression. Epstein-Barr virus-encoded ribonucleic acid testing and clonality analysis, eventually complemented with close clinical follow-up, should be performed for suspicious inflammatory lesions in older patients.