bims-myxlip 2026-05-31 papers

Issue of 2026–05–31
two papers selected by
Laura Mannarino, Humanitas Research

Int J Clin Oncol. 2026 May 27.

What are the surgical and oncologic outcomes, as well as the complications, associated with pre-operative radiotherapy in patients with low-grade soft-tissue sarcoma?

Hisaki Aiba, Joan Wang, Tsuyoshi Mizuma, Gerard Powell, Peter Choong, John Slavin, Claudia Di Bella.

BACKGROUND: Surgery with radiotherapy is a standard choice for high-grade soft-tissue sarcoma; however, the indication of radiotherapy for low-grade soft-tissue sarcoma remains controversial due to an inherent low risk of distant metastasis and recurrence after surgery, as well as potential complications after surgery.
METHODS: Between 2007 and 2020, a total of 132 patients with low-grade soft-tissue sarcoma treated with pre-operative radiotherapy followed by surgical resection were examined. Pre-operative radiotherapy was administered with 50.4 Gy in 1.8 Gy fractions, with definitive surgery performed 4-8 weeks after completing pre-operative radiotherapy to allow inflammation to subside. Optimal methods for wound closure were performed by plastic surgeons, with the selective use of flap reconstructions (pedicled or free), skin grafts or direct closure.
RESULTS: Diagnoses included well-differentiated liposarcoma/atypical lipomatous tumors (n = 66), myxoid liposarcoma (n = 31), leiomyosarcoma (n = 22), and others. After en-bloc (wide) resections, 78.8% (104/132) underwent plastic reconstruction, including free flaps (51.5%), pedicled flaps (25.8%), and skin grafts (1.5%). The resection margins were R0 in 93.2% (123/132), R1 or R2 in 6.8% (9/132). The 5-year local recurrence-free rate was 99.1%, and distant metastasis-free survival was 90.6%, with nine metastases observed, mainly in myxoid liposarcoma. The disease-specific survival at 5 years was 99.2%. Wound complication-related reoperations occurred in 21.2% (28/132), with similar rates between direct closure (21.4%, 6/28) and plastic reconstruction (21.2%, 22/104, p = 0.705).
CONCLUSION: Although surgical and oncological outcomes were favourable, the efficacy and invasiveness of pre-operative radiotherapy should be carefully balanced based on the patients' individual background, due to the potential post-operative complications.

Keywords: Low-grade sarcoma; Plastic surgery; Radiotherapy; Soft-tissue sarcoma; Surgery

DOI: https://doi.org/10.1007/s10147-026-03059-2

J Transl Med. 2026 May 26.

Molecular mechanisms underlying liposarcoma subtype transition and proteasome-associated targeted interventions.

Jiahao Liu, Mingke Huo, Sihan Wu, Zhen Wang, Sanfei Peng, Yang Fu.

BACKGROUND: Liposarcoma (LPS) is one of the most common soft tissue sarcomas and is characterized by marked heterogeneity and a strong tendency toward recurrence. Conventional histopathologic classification mainly includes well-differentiated and dedifferentiated liposarcoma, myxoid and round cell liposarcoma, and pleomorphic liposarcoma. In recent years, molecular hallmarks, such as amplification of MDM2 and CDK4 and fusion genes including FUS::DDIT3 and CPSF6-related fusions, have become essential for accurate diagnosis and subtype assignment.
MAIN BODY: LPS development and subtype transition are driven by integrated molecular events, including 12q13-15 amplification with MDM2/CDK4 overexpression, PPARγ dysregulation, PI3K-AKT-mTOR activation, epigenetic alterations, and tumor microenvironment interactions. Together, these changes promote malignant transformation, dedifferentiation, and therapeutic heterogeneity across subtypes. Within this broader framework, the proteasome has emerged as a therapeutically relevant regulatory layer, particularly in selected contexts such as MDM2-amplified WDLS/DDLS, where protein turnover directly influences the stability of key driver proteins. Clinically, complete surgical resection remains the standard treatment when feasible, while doxorubicin plus ifosfamide is the mainstay for advanced or metastatic disease. Targeted therapies, such as palbociclib for MDM2-amplified WDLS/DDLS, as well as immunotherapy, have shown activity in some patients. Emerging investigational strategies also seek to target MDM2-p53, CDK4/6, epigenetic dysregulation, and proteostasis-related vulnerabilities.
CONCLUSION: This review summarizes the classification, subtype-specific characteristics, molecular mechanisms, treatment strategies, and prognosis of LPS, and further discusses how proteasome-associated mechanisms may create therapeutic vulnerabilities in selected subtypes. A better understanding of the molecular basis underlying tumor initiation, progression, and subtype transition may support the development of more precise and mechanism-based therapeutic strategies for LPS.

Keywords: CDK4; Dedifferentiation; Liposarcoma; MDM2; Proteasome; Soft tissue sarcoma; Targeted therapy; Tumor microenvironment

DOI: https://doi.org/10.1186/s12967-026-08320-w