Current diagnostics and treatment of fibrosarcoma -perspectives for future therapeutic targets and strategies

Abstract

Adult-type fibrosarcoma is a rare and highly aggressive subtype of soft tissue sarcomas. Due to the existence of other spindle-cell shaped sarcomas, its diagnosis is always one of exclusion. The likelihood of misdiagnoses between similar tumour entities is high, and often leads to inappropriate tumour treatment. We summarize here the main features of fibrosarcoma. When fibrosarcoma is appropriately diagnosed, the patient`s overall prognosis is generally quite poor. Fibrosarcoma is characterized by its low sensitivity towards radio- and chemotherapy as well as by its high rate of tumour recurrences. Thus it is important to identify new methods to improve treatment of this tumour entity. We discuss some promising new directions in fibrosarcoma research, specifically focusing on more effective targeting of the tumour microenvironment. Communication between tumour cells and their surrounding stromal tissue play a crucial role in cancer progression, invasion, metastasis and chemosensitivity. The therapeutic potential of targeting the tumour microenvironment is addressed.

Keywords: fibrosarcoma; matrix metalloproteinases (MMPs); therapeutic resistance; tumor microenvironment.

Figure 1. Histology and MRT of a typical case of an adult fibrosarcoma (FNCLCC grade 2)

(A) Classical “herringbone” pattern and collagenous stroma. (B) More storiform area with lesser collagen content in the same tumour. Bar = 50 µm. (C) = Higher magnification showing mitotic activity. (D) = Positive Vimentin-immunohistochemistry. Other markers including EMA, pancytokeratins, α-SMA, desmin, S100, CD34 and CD117 were negative. Bar = 20 µm. (E) Magnetic Resonance Imaging of this patient shows a large hyper-intense tumor lesion in the left upper arm with infiltration und compression of the muscles and the brachial vessels and plexus.

Figure 2. The figure shows three different approaches to improve the chemosensitivity of fibrosarcoma

This includes the application of TIMP-1-GPI, the suppression of potential chemoresistant cancer stem cells (CMCs) and the interruption of CAM-DR by homotrimeric collagen type I degradation. The above figure further summarizes the pros (+) and cons (−) of each approach. CAM-DR (cell adhesion mediated drug resistance), CSCs (cancer stem cells), ↓ (reduction),↑(increase).