Citations 2
Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways
Agostini, Ludovico , Pietrantoni, Alberto , Valeri, Federico , Costanza, Flavia , Buffoli, Barbara , Piazza, Amedeo , Poliani, Pietro Luigi , Peris‐Celda, Maria , Iavarone, Federica , Gaudino, Simona , Gessi, Marco , Schinzari, Giovanni , Mattogno, Pier Paolo , Marinis, Laura De , Pontecorvi, Alfredo , Fontanella, Marco Maria , Lauretti, Liverana , Doglietto, Francesco , Buffoli, Barbara , Piazza, Amedeo , Iavarone, Federica , Gaudino, Simona , Mattogno, Pier Paolo , Fontanella, Marco Maria , Lauretti, Liverana , Doglietto, Francesco , Serioli, Simona , Chiloiro, Sabrina , Giampietro, Antonella , Rindi, Guido , Olivi, Alessandro , Bianchi, Antonio
International Journal of Molecular Sciences | October 29, 2023 | Volume: 24 | Issue: 21 | Pages: 15719
Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs’ aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.
ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition
Kemps, Paul G. , Picarsic, Jennifer , Durham, Benjamin H. , Hélias‐Rodzewicz, Zofia , Hiemcke‐Jiwa, Laura S. , Bos, Cor van den , Noesel, Carel J.M. van , Laar, Jan van , Verdijk, Robert M. , Flucke, Uta , Hogendoorn, Pancras C.W. , Woei-A-Jin, Feng Jung Sherida H. , Beilken, Andreas , Ebinger, Martin , Möhle, Robert, Bornemann, Antje, Wiegering, Verena , Ernestus, Karen, Méry, Tina, Gryniewicz–Kwiatkowska, Olga , Evseev, D. A. , Gaspari, Stefania , Gessi, Marco , Tamburrini, Gianpiero , Héritier, Sébastien , Bonneau‐Lagacherie, Jacinthe, Lamaison, Claire, Farnault, Laure , Fraitag, Sylvie , Jullié, Marie‐Laure , Haroche, Julien , Allotey, Jackie, Madni, Majid, Turner, Kerry , Picton, Susan, Barbaro, Pasquale , Poulin, Alysa, Tam, Ingrid S. , Empringham, Brianna , Whitlock, James A. , Swanson, Amy A. , Suchi, Mariko, Brandt, Jon M., Yaseen, Nabeel R. , Weinstein, Joanna , Eldem, İrem , Sisk, Bryan A. , Sridhar, Vaishnavi , Atkinson, Mandy, Massoth, Lucas R. , Alexandrescu, Sanda , Yeo, Kee Kiat , Petrova‐Drus, Kseniya , Peeke, Stephen , Muñoz-Arcos, Laura , Leino, Daniel , Grier, David D. , Lorsbach, Robert B., Kumar, Ashish R. , Garg, Shipra , Tiwari, Nishant , Schafernak, Kristian T. , Henry, M M , Halteren, Astrid G. S. van , Abla, Oussama , Kumar, Ashish , Hiemcke-Jiwa, Laura , van den Bos, Cor , van Noesel, Carel J M , van Laar, Jan A M , Verdijk, Robert M , Flucke, Uta E , Hogendoorn, Pancras C W , Woei-A-Jin, F J Sherida H , Sciot, Raf , Beilken, Andreas , Feuerhake, Friedrich , Ebinger, Martin , Fend, Falko , Wiegering, Verena , Gryniewicz-Kwiatkowska, Olga , Dembowska-Baginska, Bozenna , Evseev, Dmitry A , Potapenko, Vsevolod , Baykov, Vadim V , Gaspari, Stefania , Rossi, Sabrina , Gessi, Marco , Tamburrini, Gianpiero , Héritier, Sébastien , Donadieu, Jean , Farnault, Laure , Fraitag, Sylvie , Jullié, Marie-Laure , Collin, Matthew , Turner, Kerry , Barbaro, Pasquale M , Tam, Ingrid S , El Demellawy, Dina , Empringham, Brianna , Raghunathan, Aditya , Suchi, Mariko , Weinstein, Joanna L , Eldem, Irem , Sisk, Bryan A , Massoth, Lucas R , Hornick, Jason L , Alexandrescu, Sanda , Yeo, Kee Kiat , Petrova-Drus, Kseniya , Peeke, Stephen Z , Muñoz-Arcos, Laura S , Leino, Daniel G , Grier, David D , Roy, Somak , Kumar, Ashish R , Henry, Michael M , van Halteren, Astrid G S , Abla, Oussama , Diamond, Eli L , Emile, Jean-François , Picarsic, Jennifer L , Schafernak, Kristian , Durham, Benjamin , Wetering, Marianne D. van de , Sciot, Raf , Rossi, Sabrina , Collin, Matthew , Raghunathan, Aditya , Hornick, Jason L. , Diamond, Eli L. , Emile, Jean‐François
Blood | November 2, 2021 | Volume: 139 | Issue: 2 | Pages: 256-280
Abstract ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.