20.3: Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further mutations in K-ras and p53 genes trigger the progress of a benign tumor into a malignant tumor. At the advanced stages of tumor progression, mutations in DCC and other related genes may contribute to tissue invasion and metastasis.
As the cancer cells progress, they tend to escape the cell cycle regulation and increase their growth rate. However, such cells do not divide faster than usual. They merely continue to divide uncontrollably without undergoing terminal differentiation and apoptosis. In other words, the cell cycle in such cells skip the resting G0 phase and progress directly from the M phase to the G1 phase. Cancer cells also overcome contact inhibition, a property of normal cells to stop cell division upon coming in contact with other cells. This allows cancer cells to pile up on top of one another, forming a tumor mass.
In the 1990s, sophisticated molecular biology tools identified three important gene groups that play a critical role in cancer progression. The first group includes genes involved in cell growth and survival. The second group comprises genes involved in maintaining genetic stability, such as DNA repair enzymes. The third group of genes is involved in tissue invasion and metastasis; examples include the genes encoding cell adhesion proteins, proteolytic enzymes, and angiogenesis factors. However, no single gene is found mutated in every human cancer.