Cancer dormancy

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Dormancy is a stage in cancer progression where the cells cease dividing but survive in a quiescent state while waiting for appropriate environmental conditions to begin proliferation again. Quiescence is the state where cells are not dividing but at arrest in the cell cycle in G0-G1. Dormant cancer cells are thought to be present in early tumor progression, in micrometastases, or left behind in minimal residual disease (MRD) after what was thought to be a successful treatment of the primary tumor.

Cancer dormancy is not yet fully understood, but some researchers have performed mathematical modeling to explain the occurrence of cancer dormancy as a characteristic of all migrating tumor cells as part of an evolutionary process of selection and mutation. Recently, scientists from Aga Khan University Pakistan, have extended the studies of encystation in Acanthamoeba to induce dormancy in Prostate cancer cells lines and understanding of the signalling pathways that are involved. This eukaryotic encystation in Acanthamoeba spp., is known to involve a crosstalk between the trophozoite form of the cell and unfavourable microenvoirment that induces it. It is thought that once tumor cells disseminate and begin to migrate to a new site to metastasize, the interaction of the tumor cells with that microenvironment determines whether the cells will proliferate and form metastases or undergo growth arrest and enter cancer dormancy. It is suggested that the disseminated cells choose dormancy when the new environment is not permissive in situations such as cellular stress or a lack of available growth factors. These dormant cells can stay in this state for long periods of time and can be clinically undetectable. However, these cells can be dangerous because they can strike back years after the doctor and patient believe the patient is cured. They can exist in a quiescent state for many years, but the dormancy period can be interrupted to start proliferating uncontrollably and form metastases that cannot be treated. Cancer dormancy is often associated with minimal residual disease (MRD) where some tumor cells are left behind after a treatment and can persist either at the primary tumor site or as disseminated cells that are proliferating or dormant. MRD has been found in a widespread range of cancers including but not limited to: breast, prostate, colon, gastric, colon, pancreatic, head and neck, neuroblastoma, leukemia, melanoma, and others. These cells are often found in the bone marrow, but are also found in other organs and usually indicate poor prognosis for the patient.

One model dubbed DINOMIT (Disjunction, Initiation, Natural selection, Overgrowth, Metastasis, Involution, Transition), proposed by researchers at the Moores Cancer Center at the University of California, San Diego, has vitamin D and calcium in adequate levels playing a crucial role in potentially preventing the onset of cancer (Disjunction) as well as allowing a developed cancer to enter and stay in a weak or fully dormant state (Involution and Transition stages). "It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL (100–150 nmol/L) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial." July 2009 Volume 19, Issue 7, Pages 468–483; Vitamin D for Cancer Prevention: Global Perspective; Cedric F. Garland, Dr PH, FACE, Edward D. Gorham, MPH, Sharif B. Mohr, MPH, Frank C. Garland, PhD.

Cancer dormancy can refer to two different types: tumor mass dormancy and cellular dormancy.

Although the mechanism of signaling in cancer dormancy is also poorly understood, there is evidence of many different signaling pathways that are involved in the switch between proliferation and dormancy. The signaling most likely comes from the microenvironment. The switch seems to be mediated by interactions between surface receptors such as uPAR and integrins, mitogenic signaling from the Ras-extracellular signal-regulated kinase (ERK) pathway, and stress induced signaling from the p38 pathway. One example that has been extensively researched is the balance between the ERK pathway and p38 pathway. The ERK pathway has a major role in many cellular processes, but in cancer dormancy it is thought to be involved in mitogenic signaling that results in heightened proliferation. The p38 pathway is thought to be involved in cell cycle arrest and induction of apoptosis. Thus, a higher ERK/p38 ratio usually indicates proliferation and a lower ratio causes dormancy.

The push for understanding the mechanism of cancer dormancy is important for several clinical reasons. These dormant cancer cells are often untreatable due to drug resistance. These cells are usually resistant to chemotherapy because they are not dividing, and chemotherapy best targets rapidly diving cells.

This page was last edited on 13 September 2015, at 21:34.
Reference: https://en.wikipedia.org/wiki/Cancer_dormancy under CC BY-SA license.

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