The Cancer Stroma and Its Relevance to Tumor Survival and Treatment

Current cancer research focuses mainly upon the cancer cells in malignant tumors and is providing an expanding database about aberrations in their genetic composition. However, solid tumors also contain non-cancerous host tissue, referred to as the stroma, which plays an active and indispensable role in tumor growth and influences the virulence of the neoplasm towards the host. So far, little attention has been given to this important component of the tumor although progress in cancer therapy has been glacially slow and there is a need to consider alternative approaches. Many cell types inhabit the stroma, and are loosely distributed amidst apparently inert fibrous and viscous matrix material, composed of complex polysaccharides, proteins and other molecules. Actually, all of these elements are in constant turnover, and haphazard deviations from control mechanisms regulating this process, incurred during tumorigenesis, cause unpredictable evolution in the collective properties of the whole community. This chapter provides pathologic observations and data on reciprocal interactions between these stromal and neoplastic cellular components of tumors and how they change during the course of the disease. Malignant progression depends upon derangement of complicated communications between different specialised lineages within the cellular society normally inhabiting the organ, and this enables rapid adaptation to changing circumstances. Opportunistic misuse of such communication networks enables tumor cells to recruit and incorporate adjacent non-neoplastic stroma into their midst and modify it, so that they may grow, infiltrate and parasitise the host. The absolute dependency of primary tumors and metastases on their diverse stromal components for survival and their insatiable need to continuously recruit more stroma to support expansion, renders them vulnerable to strategies capable of disrupting the cellular interactions needed for such recruitment. This dependency of cancer cells upon the stroma is of critical importance for cancer therapy research and proposed methods for turning this parasitic behaviour of tumors against themselves are suggested below. Research on drug delivery systems for oncotoxic agents has shown that the diffusion and active transport of molecules through the interstitial space of the stroma affects their bio-availability and therapeutic efficacy. This is an avenue worthy of exploration to enhance drug therapy. This book will also describe how the inert intercellular materials can be used as scaffolding for delivering, trapping and holding cytotoxic anticancer drugs in close proximity to cancer cells, thereby enhancing the destructive effects of these drugs upon the malignant cell population, without poisoning the host. Recognition that non-neoplastic cells of the stroma are not simply passive bystanders opens the further novel possibility of stimulating the living non-neoplastic components to deny support to the tumor cell population, thereby hindering its expansion. This new approach offers opportunities for bypassing difficulties diminishing effectiveness of current cancer therapies.