bims-myxlip 2024-04-14 papers

Issue of 2024–04–14
two papers selected by
Laura Mannarino, Humanitas Research

Cancers (Basel). 2024 Mar 29. pii: 1355. [Epub ahead of print]16(7):

Functional Classification of Fusion Proteins in Sarcoma.

Marco Wachtel, Didier Surdez, Thomas G P Grünewald, Beat W Schäfer.

Sarcomas comprise a heterogeneous group of malignant tumors of mesenchymal origin. More than 80 entities are associated with different mesenchymal lineages. Sarcomas with fibroblastic, muscle, bone, vascular, adipocytic, and other characteristics are distinguished. Nearly half of all entities contain specific chromosomal translocations that give rise to fusion proteins. These are mostly pathognomonic, and their detection by various molecular techniques supports histopathologic classification. Moreover, the fusion proteins act as oncogenic drivers, and their blockade represents a promising therapeutic approach. This review summarizes the current knowledge on fusion proteins in sarcoma. We categorize the different fusion proteins into functional classes, including kinases, epigenetic regulators, and transcription factors, and describe their mechanisms of action. Interestingly, while fusion proteins acting as transcription factors are found in all mesenchymal lineages, the others have a more restricted pattern. Most kinase-driven sarcomas belong to the fibroblastic/myofibroblastic lineage. Fusion proteins with an epigenetic function are mainly associated with sarcomas of unclear differentiation, suggesting that epigenetic dysregulation leads to a major change in cell identity. Comparison of mechanisms of action reveals recurrent functional modes, including antagonism of Polycomb activity by fusion proteins with epigenetic activity and recruitment of histone acetyltransferases by fusion transcription factors of the myogenic lineage. Finally, based on their biology, we describe potential approaches to block the activity of fusion proteins for therapeutic intervention. Overall, our work highlights differences as well as similarities in the biology of fusion proteins from different sarcomas and provides the basis for a functional classification.

Keywords: epigenetic regulators; fusion proteins; kinases; mesenchymal lineage; sarcoma; transcription factors

DOI: https://doi.org/10.3390/cancers16071355

Cancer Treat Rev. 2024 Mar 30. pii: S0305-7372(24)00049-5. [Epub ahead of print]126 102722

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Elena Palassini, Giacomo Giulio Baldi, Sara Sulfaro, Marta Barisella, Giuseppe Bianchi, Domenico Campanacci, Marco Fiore, Marco Gambarotti, Massimiliano Gennaro, Carlo Morosi, Federico Navarria, Emanuela Palmerini, Claudia Sangalli, Marta Sbaraglia, Annalisa Trama, Sebastian Asaftei, Giuseppe Badalamenti, Rossella Bertulli, Alexia Francesca Bertuzzi, Roberto Biagini, Angela Bonadonna, Antonella Brunello, Dario Callegaro, Ferdinando Cananzi, Marco Cianchetti, Paola Collini, Danila Comandini, Annalisa Curcio, Lorenzo D'Ambrosio, Tommaso De Pas, Angelo Paolo Dei Tos, Virginia Ferraresi, Andrea Ferrari, Alessandro Franchi, Anna Maria Frezza, Elena Fumagalli, Matteo Ghilli, Daniela Greto, Giovanni Grignani, Michele Guida, Toni Ibrahim, Marco Krengli, Roberto Luksch, Andrea Marrari, Marinella Mastore, Alessandra Merlini, Giuseppe Maria Milano, Piera Navarria, Maria Abbondanza Pantaleo, Antonina Parafioriti, Ilaria Pellegrini, Elisabetta Pennacchioli, Marco Rastrelli, Elisabetta Setola, Salvatore Tafuto, Salvatore Turano, Sergio Valeri, Bruno Vincenzi, Viviana Vitolo, Andrei Ivanescu, Fiammetta Paloschi, Paolo Giovanni Casali, Alessandro Gronchi, Silvia Stacchiotti.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Keywords: (neo)adjuvant chemotherapy; Angiosarcoma; Clinical management; Clinical recommendations; Localized disease; Multimodal treatment; Radiotherapy; Surgery

DOI: https://doi.org/10.1016/j.ctrv.2024.102722