This week we have selected a recent article from The Conversation contributed by Dr Francesco Crea, a clinician and research at the Open University, UK which focuses on prostate cancer dormancy. Cancer cells divide forever and that is how cancer grows and spreads. Dormancy is a stage in cancer progression where the cells stop dividing but survive in an inactive, sluggish state while waiting for appropriate conditions in the body to begin dividing and multiplying again. Here is how Dr Crea explains what happens:
---------------------------------------
Cancer has always been thought of as something that grows rapidly and uncontrollably, but this view may be wrong. New evidence suggests that cancer alternatively uses the “accelerator” and the “brake” in order to survive.
If you plot the growth of prostate cancer tumour progression over years, you get a graph that looks something like this:
The graph shows that prostate cancer cells alternate periods of rapid growth with periods of dormancy. In the above example, the tumour will grow to the point where it starts to produce symptoms and the patient seeks treatment – which usually involves cutting the tumour out.
Surgery is often effective but, for some unfortunate patients, their cancer will return. At this point it is often treated with hormone therapy and chemotherapy. But even these treatments don’t always spell the end of the cancer. For some patients, the cancer will recur after a period of dormancy.
During the periods of dormancy, which could last several years, the patient will often have no symptoms and the tumour will be undetectable using the usual diagnostic tools. Until recently, we knew very little about these periods. However, research conducted by my group and by other scientists suggests that cancer dormancy is a crucial time for tumour progression.
Dangers of cancer dormancy
To understand why dormancy is useful to cancer cells, we need to examine the factors that can stop tumour progression. Cancer cells face three main challenges to their survival and growth. First, they need to deceive the immune system, which is able to eliminate most tumours. Second, they need to survive anti-cancer therapies, and, third, they need to invade distant organs and generate metastases.
Cancer dormancy is essential to meet all these challenges. During the periods of dormancy, cancer cells reshape their genetic make-up and get ready for the next stage of progression. Without dormancy, cancer cells would not be able to survive in a new environment or become resistant to the attacks of the immune system. So it is important to learn how to detect dormant cancer cells, and how to kill them.
Detecting dormant cells is not easy, though. Dormant tumours are often small and don’t produce symptoms, so patients are often unaware of them and conventional diagnostic tools are unable to “see” them. Also, dormant cancer cells are often in slow-metabolism mode, like hibernating animals. So even some sophisticated diagnostic techniques, such as PET scans, often overlook dormant tumours.
Detection and treatment
So how do we detect these dangerous sleeping cells? Fortunately, new studies are shedding light on the characteristics of dormant cancer cells. For example, our research, in collaboration with the BC Cancer Agency in Canada, has looked at the RNA produced by dormant and proliferating cancer cells. RNA is a very important molecule that carries the genetic information from DNA (the blueprint) to proteins (the cells’ workhorses).
We have shown that some small RNAs are specifically expressed by dormant cancer cells. Since these RNAs can be measured in urine and blood samples, we, and others, are trying to develop new diagnostic tools to detect these molecules. If we are successful, we will be able to develop blood or urine-based diagnostic kits that will help doctors identify dormant tumours before they become too big to effectively treat.
Once dormant cancer cells have been identified, they need to be eliminated. Unfortunately, since these cancer cells are metabolically inactive, they are less likely to be killed by conventional chemotherapy, so targeting them is difficult. Difficult, but hopefully not impossible.
A number of new studies show that dormant cells might have weak spots. For example, experiments have shown that some nonsteroidal anti-inflammatory drugs could stop dormant cancer cells that generate metastasis from “waking up”. If these results are confirmed by clinical trials, we will soon be able to offer the patients treatments that specifically target dormant cancer cells.
Francesco Crea, Lecturer in Life Sciences, The Open University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
---------------------------------------
Prostate cancer cells like travelling to the bone where they metastasize, a devastating and incurable complication. With the support of Movember Foundation PCFA funds a major, five-year study aiming at understanding what triggers the dormant cells to wake up. Prof Peter Croucher at the Garvan Institute in NSW has brought together world experts from different fields, including bone cancer, genetics and breast cancer, as well as prostate cancer clinicians, in order to solve this critical problem. For the first time, the team has developed a way to identify dormant cells inside bones under experimental conditions. They can now identify where dormant cells reside in bone and can collect the dormant cells to study how their genes change when the cells wake up. Prof Croucher and his colleagues will collect dormant cells and bone tumours from patients to study how cancer genes change in patients receiving treatment for prostate cancer. They will also identify how bone cells and immune cells may control dormant cells, and whether drugs that affect the bones and immune system may stop dormant cells from waking up. These discoveries aim to revolutionise the treatment and life of prostate cancer patients by findings new ways to prevent cancer growth in bones.
