Novel Agents and Treatments in Leiomyosarcoma

Dear Colleagues,

Leiomyosarcoma (LMS) is a rare and biologically heterogeneous sarcoma associated with high rates of recurrence and poor outcomes in the advanced setting. Despite sustained international efforts to refine systemic treatment strategies in both localized and metastatic disease, optimal treatment algorithms remain ill-defined, and survival gains have been modest. The marked clinical and molecular heterogeneity of LMS strongly suggests that distinct biological subgroups may benefit from different therapeutic approaches.

Beyond biological heterogeneity, the anatomical site of origin represents a major determinant of clinical behavior, therapeutic complexity, and outcome. The management of extremity and trunk LMS differs substantially from that of retroperitoneal or uterine LMS, particularly with respect to surgical planning, locoregional control strategies, recurrence patterns, and integration of systemic therapy. These site-specific differences create unique therapeutic challenges and may influence both prognosis and trial design.

Particular attention must be devoted to uterine leiomyosarcoma (uLMS), which represents not only a biologically distinct subset but also a uniquely challenging clinical entity. In uLMS, preoperative diagnosis remains problematic, as differentiation from benign leiomyomas or tumors of uncertain malignant potential can be difficult despite modern imaging. This diagnostic uncertainty may directly impact surgical management and oncologic outcomes. Moreover, uLMS displays specific molecular features, including emerging evidence of homologous recombination repair defects and alterations in BRCA1/2 and related pathways, potentially defining subgroups amenable to DNA damage–targeting strategies such as PARP inhibition.

This Special Issue focuses on innovative concepts and emerging data aimed at advancing the development of novel agents and treatment strategies specifically for leiomyosarcoma, with dedicated attention to uterine LMS as a distinct clinical and translational entity. We seek contributions that support rational, biology-driven drug development, including approaches that leverage insights from other tumor types and translational research to accelerate progress in LMS. Submissions may include original clinical, translational, or preclinical research, as well as high-impact reviews.

Preferred topics include, but are not limited to, the following:

• Identification and validation of novel therapeutic targets in leiomyosarcoma;
• Site-specific management strategies in extremity, retroperitoneal, and uterine LMS;
• Molecular stratification distinguishing uterine versus extra-uterine LMS;
• Preclinical rationale for novel agents or drug combinations, including therapies developed in other malignancies with potential relevance to LMS;
• Biomarker-driven precision oncology approaches, including subgroup-specific strategies;
• Innovative immunotherapy concepts and rational combinatorial approaches;
• Novel clinical trial designs and endpoints aimed at accelerating drug development in leiomyosarcoma (e.g., platform or adaptive trials);
• Leiomyosarcoma-specific treatment algorithms;
• Translational correlatives and results from ongoing or completed clinical trials.

High-quality submissions addressing other aspects of leiomyosarcoma treatment and drug development are also welcome.

Dr. Elise F. Nassif Haddad
Dr. Roberta Sanfilippo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• leiomyosarcoma
• uterine leiomyosarcoma
• STUMP
• retroperitoneal leiomyosarcoma
• targeted therapies
• precision medicine
• immunotherapy
• drug development
• clinical trials
• translational oncology