biostudies-literatureLongo VItalian Ministry of Health3237https://www.ebi.ac.uk/biostudies/studies/S-EPMC10970296biostudies-literatureUnknown25(6)Recently, the fifth edition of the WHO classification recognized the thoracic <i>SMARCA4</i>-deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with <i>SMARCA4</i> 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.International journal of molecular sciencesTreatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go.PMC10970296deliberation 187/2023Montagna ESGaletta DPesola FNardone APerrone AMontrone MGesualdo MMarech ILongo VCatino APizzutilo PfalseTreatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go.Recently, the fifth edition of the WHO classification recognized the thoracic <i>SMARCA4</i>-deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with <i>SMARCA4</i> 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.2024-01-01T00:00:00Z2024 Mar2025-04-21T21:27:28.431Z2025-04-05T18:22:12.785ZS-EPMC109702963854221110.3390/ijms25063237