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What is cancer?
Cancer is currently the second leading cause of death worldwide after cardiovascular diseases.
In 2020 there were more than 19 million of new cases of cancer and almost 10 million deaths. But the numbers keep rising, in 2022 are expected to be around 20 million new cases and more than 10 million deaths, and by 2040 the number of new cases and deaths will be 56,7% and 63,7% more than the 2020 numbers.
Cancer is a multifactorial disease where cells in a specific part of the body grow uncontrollably invading and destroying surrounding healthy tissues including organs. Sometimes these cells can spread to other parts of the body, this is the process known as metastasis.
Carcinogenesis
Carcinogenesis can be generically described as the process where a normal healthy cell turns into a cancer cell due to the action of a carcinogen on chromosomal DNA.
Even though it can happen in other events of the cell cycle, it is during the division process that the cell is more susceptible to the action of a carcinogen.
Carcinogens are all around us and within us and are grouped in:
Primary determining factors:
- Includes chemical substances, physical factors and biological factors, these factors are notorious for acting directly on DNA and RNA (ex: Arsenic, Nitrosamines, UV radiation, polycyclic aromatic hydrocarbons present in cigarette smoke)
Secondary determining factors:
- Some people have an increased risk of cancer due to hereditary determinism
Favoring factors:
-Risk factors that even if non-relational to carcinogens were observed in the incidence of tumors (ex: age, sex, nutritions, etc)
Several theories were proposed to explain this process but the most commonly accepted and experimentally demonstrated is the Multistage carcinogenesis theory which is divided into three stages: Initiation, Promotion and Progression.
Initiation
It starts when the carcinogen induces a lesion on chromosomal DNA that if not repaired it will be replicated into new cells, also called initiated cells.
This stage also leaves the initiated cell with proliferative capacities that can remain potential and latent and stay in this state indefinitely.
The action of a carcinogen for itself does not lead directly to cancer, it changes the cell permanently and is irreversible, interestingly it was demonstrated that repeated doses of an initiator resulted in an additive number of tumors produced.
Promotion
Unlike initiators, a promoter usually does not cause a carcinogenic response by itself, it produces a carcinogenic response if applied several times after just a single dose of an initiator.
A substance capable of acting as an initiator and promoter at the same time is known as a complete carcinogen.
Progression
In this stage, the cells that grew into a tumor during the previous stages turn into a malignant tumor, this transformation involves several steps such as oncogene activation, chromosome aberration, genetic changes, etc.
The tumor has a rapid proliferation rhythm and invasive and metastasizing abilities and can also continue to increase its malignancy.
Common genes involved
Many genes were found to be linked to cancer, contributing to its development, divided into two categories:
Tumor suppressor genes
Known to be protective genes, tumor suppressor genes are responsible for limiting cell growth by repairing some DNA mistakes, monitoring cell growth, and controlling cell death.
When these genes mutate, cells grow uncontrollably and turn into a tumor.
Ex: BRCA1, BRCA2, p53 or TP53
p53 is the most commonly mutated gene in people with cancer.
Oncogenes
These genes, when activated, turn healthy cells into cancerous cells.
Ex: HER2 and RAS family of genes
DNA repair genes
Genes that fix mistakes made when DNA is copied, many of these genes act as tumor suppressor genes.
If DNA mistakes are not repaired, they will become mutations that can lead to cancer.
Many DNA repair genes act as tumor suppressor genes such as BRCA1 or p53.
My current work
One particular approach to stop cancer proliferation is to understand the mechanisms used by the cells and stop them.
That is exactly what I am currently doing, let me tell you more:
The cell behavior towards certain substances allows scientists to understand more about how they interact.
The substance that I am now studying is zinc, a vital metal to a healthy organism, found highly concentrated in the prostate cells.
The role of zinc both in healthy prostate cells and prostate cancer cells has been studied and two major functions were concluded:
In a healthy prostate, cells use zinc to produce citrate, a component of sperm fluid, and to stop cell proliferation as it is not needed, so the cell will spend its energy producing citrate.
But in men with prostate cancer it was found that prostate cells had low to no amounts of zinc, meaning that cell proliferation will not be stopped and since the cell is not spending its energy in producing citrate, it will then spend it in proliferation.
Cell proliferation occurs when the cell membrane receives a specific signal for proliferation and that signal is carried to the cell nucleus by a signalling pathway, a highway of proteins that consecutively carry the signal to the nucleus.
Several studies demonstrated that zinc is responsible for suppressing these events in more than one pathway. There are many of these pathways making it difficult to completely understand the role of this metal since it act differently in each one.
We are focusing on one particular pathway that we believe is highly affected by zinc, and considering that prostate cancer cells show a loss of zinc, we believe that it causes an increased proliferative and survival capacity of prostate cancer cells.
The project that I am currently working in seeks to investigate the molecular mechanisms by which Zinc suppresses the proliferative signalling in prostate cells and how loss of this suppression affects the growth and survival of prostate cancer cells.
Thank you for your interest!
João Miguel Gomes Tomás
References
Baba, A. I., & Câtoi, C. (2007). CARCINOGENESIS. https://www.ncbi.nlm.nih.gov/books/NBK9552/
Costello, L. C., & Franklin, R. B. (2016). A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Archives of Biochemistry and Biophysics, 611, 100–112. https://doi.org/10.1016/J.ABB.2016.04.014
Council, R., & Thomas, R. D. (2023). Mechanisms of Carcinogenesis. Nih.gov; National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK219109/
Global Cancer Observatory. (n.d.). Retrieved February 3, 2023, from https://gco.iarc.fr/
NHS Choices. (2023). Overview - Cancer. https://www.nhs.uk/conditions/cancer/
The Genetics of Cancer. (2012, March 26). Cancer.net. https://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/genetics-cancer
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