Targeting the cancer microenvironment
With clinical research placing so much emphasis on the genetics of cancer, predictive biomarkers and the identification of molecular targets in tumour cells, it’s all too easy to forget that cancer cells also have ‘context’.
- Date: 01 Oct 2012
- Topic: Anticancer agents & Biologic therapy
Dr Giuseppe Curigliano from the European Institute of Oncology, Milan, Italy, made the strong case for more research to be performed into cancer microenvironments. Cancer cells interact with normal host stromal cells (e.g. endothelial cells, fibroblasts, various immune cells) with a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it.
Infiltrating immune cells can furthermore sustain proliferative signaling through the release of itogenic growth mediators. Furthermore, tumour associated macrophages may increase the metastatic potential through CSF1R signaling. It makes sense, Dr Curigliano agreed, to ‘turn on’ normal immune cells around a tumour and induce an antitumour immune response. But cancers typically escape immune surveillance by exploiting various natural mechanisms for tolerance. Cytotoxic therapies can be used to induce mammary epithelial cells to produce macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin, which together enhance CSF1 receptor (CSF1R) dependent macrophage infiltration.
Recent studies have also shown that blockade of macrophage recruitment with CSF1R-signalling antagonists, in combination with paclitaxel, could improve survival in mouse models of breast cancer, and furthermore reductions in pulmonary lung metastases have also been found.