Dr Pimenta on Ongoing Therapeutic Challenges in Soft Tissue Sarcomas

"[Broadly] across sarcomas, there's a huge opportunity to improve treatment strategies and outcomes; for liposarcoma in particular, there's an unmet need for targeted therapies."

Erica Maria Pimenta, MD, a medical oncologist and clinical fellow in medicine at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, outlined the ongoing therapeutic and translational challenges in soft tissue sarcoma, highlighting the persistent unmet need in dedifferentiated liposarcoma (DDLPS) and other subtypes lacking effective targeted therapies.

Despite incremental advances, the treatment landscape for DDLPS remains largely dependent on empiric chemotherapy, which offers limited clinical benefit and is associated with substantial toxicity. Pimenta emphasized that although agents such as anthracyclines and ifosfamide remain the standard of care, there is an urgent need to move beyond non-specific cytotoxic regimens. One key barrier to this progress is the limited understanding of the molecular drivers of disease, particularly in DDLPS, where defining actionable targets has proven difficult.

Pimenta noted that ongoing research at Dana-Farber Cancer Institute aims to expand the therapeutic armamentarium for patients with liposarcoma by interrogating molecular and epigenetic underpinnings of disease progression. This includes efforts to identify novel biomarkers and signaling pathways that may inform precision oncology approaches. Pimenta noted that, unlike more genetically tractable malignancies, DDLPS is characterized by complex karyotypes and few recurrent point mutations, which complicates the identification of druggable targets.

Current investigative efforts are examining whether transcriptomic and epigenetic dysregulation may play a more prominent role than previously appreciated. Additionally, studies are exploring the interaction between tumor biology and the immune microenvironment—particularly macrophage infiltration—which may influence immune escape and resistance to checkpoint blockade.

Although previous clinical trials evaluating immune checkpoint inhibitors and targeted therapies such as MDM2 or CDK4 inhibitors have yielded modest results, Pimenta remains optimistic that a more granular understanding of tumor heterogeneity will allow for better trial design and therapeutic stratification. She underscored the importance of continuing to build comprehensive translational frameworks that integrate molecular profiling, preclinical modeling, and biomarker-driven trial development.