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Repopulation of Cancer Cells

© David Olle

Nature of Tumors

Tumor cells require a steady supply of oxygen and nutrients in order to grow and flourish, just like normal cells. When the tumor is small, the tumor cells are well-nourished by being in close proximity to blood vessels. As the tumor grows, however, many cells migrate away from the blood vessels. These more distant cells are hypoxic (oxygen-deficient), and lack access to nutrients. 1 As a result, these cells are slower growing, and can even become dormant.

The Effect of Radiation and Chemotherapy on Tumor Cells

Both radiation and chemotherapy act on rapidly growing cells and can show good initial success in killing those cells. However, radiation is not very effective on hypoxic cells, and chemotherapeutic drugs have difficulty in reaching cells more distant from blood vessels. The surviving tumor cells will repopulate after treatments, or during intervals between treatments. Typically, there is a lag phase after initial treatments when no new tumor growth is apparent. The rate of regrowth tends to accelerate after each successive treatment, and the success or failure of treatment is directly related to the rate of repopulation. It should be noted that this phenomenon will take place independently of any development of drug resistance.

Treatment Strategies to Inhibit Repopulation

Radiotherapy

Accelerated fractionation of radiotherapy seeks to reduce the overall treatment time, thereby providing less opportunity for repopulation of tumor cells. 3With this approach, radiation treatments are given as frequently as three times per day, including weekends. This procedure allows greater normal tissue recovery to occur during the intervals between treatments. This procedure has been beneficial in controlling Burkitt's lymphoma and non-small cell lung cancer.

Chemotherapy

Chemotherapy treatments given at 2-week rather than longer intervals have shown improved survival of patients with breast cancer, non-Hodgkin's lymphoma and bladder cancer. The trials did not result in increased toxicity in normal tissues.

There have been several trials in which chemotherapy has been given after initial radiotherapy. This procedure resulted in improved survival from many cancers. The tolerated dose of chemotherapeutic drugs is small, however, and its use may be limited to cases where there is a rapid repopulation of tumor cells.

Molecular-targeted cytostatic agents

Repopulation of tumor cells is largely dependent on molecular signaling pathways. The molecular signaling pathway begins with a growth factor (a protein or peptide) binding to a specialized receptor located on the cell surface membrane. This binding induces activation of tyrosine kinase enzyme that is associated with the receptor. The activated tyrosine kinase initiates the formation of a cascade of molecular intermediates. The final step is the binding of a molecule to a gene of nuclear DNA. This binding activates the gene, forming a protein necessary to complete the cell cycle leading to multiplication of tumor cells. 4