Dormancy is a stage in the development of cancer in which cells stop dividing but survive in silence while waiting for appropriate environmental conditions to start proliferation again. Quiescence is a state in which cells do not divide but on capture in the cell cycle in G0-G1. Inactivated cancer cells are thought to be present in early tumor development, in micrometastasis, or left behind in minimal residual disease (MRD) after what is considered a successful treatment of primary tumors.
Video Cancer dormancy
Mechanism
Occurrence in cancer
Cancer dormancy is not yet fully understood, but some researchers have modeled mathematics to explain the occurrence of cancer dormancy as a characteristic of all migrating tumor cells as part of the evolutionary process of selection and mutation. Recently, scientists from Aga Khan University of Pakistan, have expanded the study of coding at Acanthamoeba to induce dormancy in prostate cancer cell lines and an understanding of the signaling pathway involved. This eukaryotic dilution in Acanthamoeba spp., Is known to involve crosstalk between the trophozoite cell form and the unfavorable microenvoirment that causes it. It is thought that once tumor cells spread and begin to migrate to a new site to metastasize, the interaction of tumor cells with the microenvironment determines whether the cells will proliferate and form metastases or undergo growth capture and enter cancer dormancy. It is suggested that disseminated cells choose dormancy when the new environment is not permissive in situations such as cellular stress or lack of available growth factors. These dormant cells can stay in this country for long periods of time and can be clinically undetectable. However, these cells can be dangerous because they can strike back years after doctors and patients believe that the patient has recovered. They can exist in silence for many years, but the dormancy period can be disrupted to begin proliferating uncontrollably and forming untreatable metastases. Dormancy of the cancer is often associated with minimal residual disease (MRD) in which some tumor cells are left behind after treatment and can survive either at the site of the primary tumor or as a spreading cell that breeds or dormant. MRD has been found in a wide range of cancers including but not limited to: breast, prostate, colon, stomach, colon, pancreas, 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 a poor prognosis for the patient.
A model called 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 at an adequate level of play an important role has the potential to prevent the occurrence of cancer (Disjunction) and allows cancer developed to enter and live in a weak or completely dormant country (Involution and Transition Stage). "It is projected that raising a minimum serum level of 25 years (OH) D to 40 to 60 ng/mL (100-150 nmol/L) would prevent some 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three quarters of deaths from the disease in the United States and Canada, based on observational studies combined with randomized trials. "July 2009 Volume 19, Issue 7, Page 468-483; Vitamin D for Cancer Prevention: A Global Perspective; Cedric F. Garland, Dr PH, FACE, Edward D. Gorham, MPH, Sharif B. Mohr, MPH, Frank C. Garland, PhD.
Cancer dormancy types
Cancer dormancy may refer to two different types: dormancy of tumor mass and cellular dormancy.
- In the dormancy of tumor mass, the tumor mass will continue to divide until it is physically limited by size, has no access to blood supply, or the immune system works on it. Here the cells are not completely inactive, but they can not expand and sit in a balance between proliferation and apoptosis. The emerging Hippo (Hpo) signal path is thought to be responsible for controlling the size of the organs, inhibition of cell contact, and tumorigenesis by stopping cell proliferation and increasing cell death. Dormansi mass of the tumor is also often associated with angiogenic dormancy. This occurs when the tumor enters a state of hypoxia because they can not get blood vessels. If the number of cells still proliferating is equal to the dead number of no blood supply, the tumor is in angiogenic dormancy.
- Cellular Dormancy refers to cells entering a quiescence state where growth is captured in G0-G1 from the cell cycle, and cells are completely inactive and asymptomatic. It is called a dormancy that tumor cells enter when they survive dissemination but can not immediately adapt to pressure or new micro environments. More recently, the pathogenic eukaryotic cell encoding model has been associated with dormancy of cancer cells, Acanthamoeba spp. studied for conditions leading to their encystation. This condition is imposed on prostate cancer cells to induce a state of dormancy from which they can be revived with the removal of provoking stimuli. Dormant cells may also have different mechanisms that can be used to avoid an immune response.
The signaling path
Although the mechanism of signaling in cancer dormancy is also poorly understood, there is evidence from many different signaling pathways involved in the transition between proliferation and dormancy. The most likely signal comes from the micro environment. This switch appears to be mediated by interactions between surface receptors such as uPAR and integrins, mitogenic signaling of the extracellular Ras-Rule signal-regulated kinase (ERK) pathway, and stress induced signals from p38 pathways. One of the most studied examples is the balance between the ERK line and the p38 line. The ERK pathway plays a major role in many cellular processes, but in dormancy the cancer is thought to be involved in a mitogenic signal that produces high proliferation. The p38 path is considered to be involved in cell cycle capture and apoptotic induction. Thus, a higher ERK/p38 ratio usually indicates proliferation and a lower ratio causes dormancy.
Maps Cancer dormancy
Clinical and therapeutic interest
The drive to understand the mechanism of cancer dormancy is important for several clinical reasons. These inactive cancer cells are often untreatable due to drug resistance. These cells are usually resistant to chemotherapy because they do not divide, and chemotherapy targets rapid cell diving.
- The idea for a therapeutic strategy is to induce cancer cells to be induced or maintained in an inactive state. By inducing normally untreatable malignant cells into growth capture, patients will be able to survive under chronic asymptomatic conditions. This can be achieved by finding the exact mitogenic signal ratios such as ERK to p38. However, although cells can remain active for long periods of time, there is always a risk of dormancy disorder leading to metastasis even by the smallest change in the signaling network. Another therapeutic strategy is to develop methods to paralyze cells that are not fully active.
- By targeting the mechanisms behind the inactivity of inactive cells and how they acquired drug resistance, it is possible to induce this inactive cell until death.
- Finally, it is hoped that understanding the dormancy mechanism will enable researchers to discover potential dormancy markers that may contribute to determining patient prognosis.
Question left
There are many questions that still need to be answered in an effort to understand the dormancy of cancer more fully. Some of them include:
- What is the real cause of the inactivation of inactive cancer cells?
- How similar to inactive cancer cells and cancer stem cells?
- Is the cancer dormancy mechanism different for different types of cancer?
- Are all long-term cancer survivors free from relapse also have cancer cells that are dormant hidden somewhere?
Finally, it is important for scientists to use models that can more accurately model the stage of cancer dormancy to find the mechanism. By more fully understanding the mechanisms of cancer dormancy, it will be possible to find new therapeutic strategies to target these non-active cancer cells. Maybe the body does not completely get rid of cancer cells in a way that might be considered "cured" with complete elimination, but it is an alternative "operational healing" in which patients control chronic illness so they will eventually die with their cancer instead of it.
References
Source of the article : Wikipedia
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