Targeted Therapy in Sarcoma

Dear Colleagues,

Sarcomas are a rare group of heterogeneous malignancies that originate in mesenchymal tissues. Their rarity and heterogeneity make sarcomas an ongoing challenge for clinicians in an interdisciplinary setting, including in surgery, oncology, and radiotherapy. Many subtypes show limited sensitivity to conventional chemotherapies, leading to high recurrence rates after surgery and a high mortality rate overall. Thus, to this day, radical resection remains key in the multidisciplinary treatment of sarcomas, with R0 resection providing the best outcomes, even in advanced stages. Sarcomas can start to develop in many locations, including the abdomen, retroperitoneum, extremities, fat tissue, muscles, bones, and connective tissues. Given this anatomic distribution, sarcomas are a challenging field for both surgeons and oncologists. While some tumors are driven by well-defined isolated mutations or chromosomal translocations, which give rise to fusion proteins, others feature several genomic aberrations that generate a more complex phenotype.

Targeted therapies against specific driver mutations or the resulting proteins have revolutionized many therapeutic approaches in other malignancies, especially in gastrointestinal stromal tumors (GIST), a subtype of sarcomas. Some tyrosine kinase inhibitors (TKI) that are used in other fields of oncology, such as pazopanib, have been tested in preclinical settings, as well as in clinical trials, with promising results. In addition, the combination of targeted therapies together with immunotherapy, e.g, TKIs together with checkpoint blockades, has been used to investigate some subtypes of sarcomas in clinical trials.

While molecular-targeted therapy is promising, today, surgical therapy still provides the best outcomes for patients with sarcoma. Considering this situation, targeted surgical approaches are also of interest. For example, fluorescence-guided operations that use ICG are thought to improve oncological outcome, in addition to sparing healthy tissue, and thereby reducing post-operative morbidity. Furthermore, intra-operative image guidance can be used to reduce positive resection margins, which improves the prognosis of sarcoma patients.

Taken together, targeted therapies for specific subtypes of sarcomas are still not clearly established and far more research is necessary, ranging from preclinical groundwork to discover new therapeutic targets, to the assessment of promising drug combinations or operative procedures in the clinic.

In this Special Issue, a collection of studies on the current state of preclinical and clinical investigations shall be assembled. Studies that investigate new promising therapeutic targets, pathways, or innovative surgical approaches, as well as submissions that evaluate targeted therapies in combination with immuno-therapy and/or conventional systemic therapies, are encouraged. The aim is to summarize the interdisciplinary nature of sarcoma treatment, with a focus on targeted therapeutic strategies.

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

• Current and new therapeutic targets in specific sarcoma subtypes;
• Diagnosis and selection of patients with sarcoma for targeted therapy;
• Targeted operative therapy;
• Individual sarcoma therapy;
• Role of the immune system in the setting of targeted therapy;
• Implications of the combination of targeted therapy with immune-therapies and/or conventional chemotherapies.

Prof. Dr. Thiha Aung
Dr. Anna Duprée
Prof. Dr. Silke Haerteis
Guest Editors

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• targeted therapy
• therapeutic targets
• targeted operative therapy
• individual sarcoma therapy
• fusion proteins
• soft tissue sarcoma
• fluorescence-guided operations
• indocyanine green