Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go

• Published in: International journal of molecular sciences Vol. 25; no. 6; p. 3237
• Main Authors: Longo, Vito, Catino, Annamaria, Montrone, Michele, Montagna, Elisabetta Sara, Pesola, Francesco, Marech, Ilaria, Pizzutilo, Pamela, Nardone, Annalisa, Perrone, Antonella, Gesualdo, Monica, Galetta, Domenico
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2024; MDPI
• Subjects: Adult; Antimitotic agents; Antineoplastic agents; Apoptosis; B cells; Biomarkers, Tumor; Brain cancer; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - therapy; Chemotherapy; clinicopathological features; Cyclin-dependent kinases; DNA Helicases - genetics; DNA repair; Health aspects; Histology; Humans; Immunotherapy; International agencies; Kinases; Liver cirrhosis; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Metastasis; Middle age; Middle Aged; Mutation; Nuclear Proteins - genetics; Proteins; Radiotherapy; Review; Sarcoma - pathology; SMARCA4-UT; Tomography; Transcription Factors - genetics; Tumorigenesis; Tumors; SMARCA4-UT; clinicopathological features; immunotherapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25063237

Recently, the fifth edition of the WHO classification recognized the thoracic
-deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with
deficiency because of the different clinicopathological characteristics of these two diseases. SMARCA4-UT mainly occurs in young to middle-aged adults and involves a large mass compressing the tissues surrounding the mediastinum and lung parenchyma. Unfortunately, SMARCA4-UT shows a high probability of recurrence after upfront surgery as well as radiotherapy resistance; moreover, chemotherapy has low efficacy. Moreover, given the recent classification of SMARCA4-UT, no data concerning specific clinical trials are currently available. However, several case reports show immunotherapy efficacy in patients with this disease not only in a metastatic setting but also in a neoadjuvant manner, supporting the development of clinical trials. In addition, preclinical data and initial clinical experiences suggest that inhibiting pathways such as CDK4/6, AURKA, ATR, and EZH2 may be a promising therapeutic approach to SMARCA4-UT.