title: Primary refractory and early-relapsed Hodgkin's lymphoma: strategies for therapeutic targeting based on the tumour microenvironment.
abstract: Classical Hodgkin's lymphoma (cHL), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of the cHL microenvironment express molecules involved in cancer cell growth and survival, such as CD30L or CD40L. Moreover, several signal transduction pathways that are critical for the proliferation and survival of neoplastic Hodgkin Reed-Sternberg (HRS) cells, including NF-κB, JAK-STAT, PI3K-AkT and ERK, are deregulated in cHL. Although most patients can be cured with modern treatment strategies, approximately a quarter experience either primary or secondary chemorefractoriness or disease relapse, thus requiring novel treatments. Preclinical and clinical evidence has elucidated a complex crosstalk between malignant HRS cells and the reactive cells of the microenvironment, which suggests that novel therapeutic approaches capable of targeting HRS cells along with reactive cells might overcome chemorefractoriness. In the near future, these novel therapies will also be tested in chemosensitive patients, to reduce the long-term toxicity of chemo-radiotherapy.
authors.affiliation: Department of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, Aviano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.affiliation: Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.affiliation: Department of Oncology and Haematology, Humanitas Cancer Centre, Humanitas Clinical and Research Centre, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Castagna
authors.affiliation: Department of Oncology and Haematology, Humanitas Cancer Centre, Humanitas Clinical and Research Centre, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Department of Oncology and Haematology, Humanitas Cancer Centre, Humanitas Clinical and Research Centre, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D014157:Transcription Factors
keywords: Hodgkin Reed-Sternberg cells; Hodgkin's lymphoma; Hodgkin's lymphoma microenvironment; chemorefractoriness; early-relapsed Hodgkin's lymphoma; microenvironment; refractory Hodgkin's lymphoma; signalling pathways; transcription factors; tumour microenvironment