The Nation's Investment in Cancer Research

Following Important Leads

Tumor Microenvironment

Much of the basic cancer research conducted over the past 30 years has been focused on the cancer cell, without particular concern for its surroundings. Researchers are finding, however, that tumor cells do not live independently. To survive and proliferate, tumors require assistance from the microenvironment of cells, molecules, and blood vessels immediately surrounding them.

“Non-cancerous cells recruited from the host are now seen as rate-limiting determinants of how well the tumor grows and how it is able to metastasize and establish itself in distant organ sites,” explained Robert A. Weinberg, Ph.D., a member of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. Dr. Weinberg discovered the first human oncogene, which directs tumor growth, as well as the first tumor suppressor gene.

At the heart of the tumor microenvironment is the signaling that goes on between cells. Research in this area is yielding evidence of a greater number of cytokines, which are proteins that guide interactions between cells. These cytokines facilitate talk between pre-cancerous cells and other cells that have been recruited to build a tumor’s framework. The basic characteristics of malignant cancers are developed and stimulated by signals originating in this framework.

Because standard research models and methods for analyzing cancer cell behavior cannot adequately capture the complex nature of the tumor microenvironment, more advanced models are now being developed, in order to realistically mimic the signaling pathways and interaction between the tumor and its surrounding environment. A highly sophisticated computer model, developed in conjunction with scientists from disciplines such as mathematics and bioinformatics, is providing a fuller picture of cancer as a biological system.

One eventual use for these so-called in silico models could be to generate a virtual model of individual patients’ tumors, then simulate how various treatments would affect the tumor and patient, pointing to the most effective and least toxic therapy. Such computer models hold great potential for studying diseases other than cancer.

Because of the fundamental importance of this area of research, NCI launched a tumor microenvironment initiative in 2006 with the funding of 10 programs, most of which are university based, and the establishment of a network to facilitate the programs. The primary objective of the initiative is to delineate mechanisms of tumor-host interactions in cancer by better understanding the role that the stroma, or supporting tissue and elements surrounding the tumor, plays in initiation, progression and metastases of a tumor.