Why Treated Cancer Recurs: Dormant Cancer Cells

One major problem after a complete cancer treatment response is the risk of recurrence many years later. What causes cancer to reappear after so long?

Tumor dormancy means cancer cells remaining undetectably "asleep" for long periods. These cells survive standard treatment and begin dividing again years later, causing recurrence.

Cancers frequently showing tumor dormancy include;

-breast cancer,

-prostate cancer,

-skin cancer (malignant melanoma) and

-B-cell lymphoma.

Dormant cancer cells have 4 main characteristics:

1. Slow growth,
2. Resistance to standard cancer treatments, 
3. Evading the immune system and
4. Self-renewal

Cell growth is controlled by a sophisticated manager. Cells must pass through G0, G1 and G2 points in sequence to divide. Those failing requirements remain at the G0 checkpoint. In other words, they do not multiply until conditions are suitable.

There are 3 tumor dormancy mechanisms:

1. Cellular dormancy: Cells remain continuously at the G0 checkpoint, so they neither divide nor multiply.
2. Angiogenic dormancy: Rapidly growing cancer cells eventually need vessels to supply nutrients. Some cannot form enough vessels. Their growth stops and a continuing balance develops between dying and growing cells, called angiogenic dormancy.
3. Immunogenic dormancy: Our immune system approaches tumors in 3 phases: elimination, equilibrium and escape. Some tumor cells adapt and learn to appear "friendly" to the immune system, remaining dormant for years. Standard cancer treatments and environmental factors can awaken them and trigger aggressive division.

Why and how tumor cells enter dormancy remain unanswered. Recent research indicates epigenetic (gene-environment relationship) factors. Similarities between dormant cells and cancer stem cells are also being investigated. If they are the same cell type, targeted treatments developed against cancer stem cells may also work against dormancy. Another question is whether all successfully treated patients still harbor dormant cancer cells.

Recent cancer research debates what strategy should be developed against dormancy.

There are basically two options;

1. Develop treatments that awaken dormant cancer cells, or
2. Treatments that keep tumors asleep?

Recent clinical studies observed that treatments awakening tumors caused cancer cells to divide more aggressively and develop multidrug resistance. The generally accepted approach is therefore to develop treatments keeping tumors dormant. Drugs targeting epigenetic factors are promising for this purpose.