When Cancer Becomes a SCANDAL

Jabale Rahmat
Junior
School of Life Sciences
Independent University, Bangladesh

March 23rd, 2019

Have you ever heard of a bacterium afflicted by cancer? Of course not. Cancer is an accidental consequence of multicellularity. Multicellular organisms, like animals, have tightly regulated numbers and distributions of many different types of cells that cooperate as a functional whole. Cancer occurs when some of these cells decide to go rebel and keep dividing even at the expense of the organism. We could think of cancers as cellular parasites.

Actual parasites are transmitted from host to host, but we obviously do not see cancers being transmitted between humans. There are, however, transmissible cancers that have been discovered in other animals, leading to some fascinating speculation on what actually distinguishes these cancers from parasites.

Metzger et al, in their 2016 paper [1], reported that mussels, cockles, and golden carpet shell clams are afflicted by independent lineages of leukemia-like transmissible cancers, adding to three other kinds of transmissible cancers that had been previously known (in dogs, Tasmanian devils, and soft-shell clams, respectively). In these bivalve species, cancerous hemocytes (the equivalent of blood cells in invertebrates) get transmitted between individuals of the same species through the water as they breathe by filtering oxygen directly from the water. In all three cases, while cancer may be occurring spontaneously with some frequency, the transmissible forms appear to be responsible for most of the cases in natural populations. Interestingly, they discovered that the golden carpet shell clams got their cancer from another clam species, the pullet carpet shell clams, suggesting a cross-transmissible event of cancer. But the pullet carpet shell clams are resistant to the cancer. This suggests that they may have evolved resistance to this transmissible cancer, owing to strong selection pressures exerted by the cancer. Adaptation like this would mirror the dynamics of host-pathogen coevolution.

A healthy Tasmanian devil. University of Tasmania

While it is difficult to know whether this was indeed an adaptation,  Epstein et al. [2] were able to ask a similar question about a transmissible cancer in Tasmanian devils in a 2016 study. The devil facial tumor disease (DFTD), the transmissible cancer found in Tasmanian devils, had been discovered in the Tasmanian island of Australia in 1996. The disease, which is lethal in virtually all cases, has since been devastating Tasmanian devil populations. The cancer is able to spread between individuals by evading and suppressing immune responses. But against all odds, the Tasmanian devils have successfully avoided extinction and managed to persist. Epstein and colleagues, in the 2016 study, investigated whether the Tasmanian devils had evolved resistance to DFTD. Using tissue samples from Tasmanian devils that were collected before and after DFTD ravaged the populations, they were able to show different populations of Tasmanian devils had undergone rapid evolution in regions of the genome containing genes related to immune function and cancer risk. This suggests that strong selection pressure imposed by the DFTD has resulted in evolution of improved defenses against the cancer in Tasmanian devils. An arms race could ensue, leading to the evolution of DFTD to avoid these new defenses.

If these transmissible cancers are genetically distinct and act essentially like parasites, why do we not think of them as distinct species? Could they perhaps represent the origin of new species? Recently, Panchin et al. proposed the SCANDAL (Speciated by CANcer Development Animal) hypothesis, which posits that speciation may sometimes arise from transmissible cancers [3].

By using bioinformatic approaches, they showed that one form of obligate parasites of fish called Myxosporea may have arisen in this manner. They provide evidence that its ancestor was a free-living cnidarian that had lost a large number of genes involved in apoptosis and tumor-suppression. They hypothesized that this loss of genes may have taken in a single somatic cell, leading to cancer, which was followed by the spread of the cancer cells to fish. This may have ultimately led to the parasitic relationship we observe today. While an attractive hypothesis, the loss of these genes may also have occurred as part of an overall simplification of the genome of the free-living cnidarian as it adapted to a parasitic lifestyle, much like how obligate intracellular bacteria tend to have reduced genome sizes.

Mechanisms of speciation remain mired in mysteries, but we can at least state with some certainty that there have been several different mechanisms at work in the evolutionary history of life on earth. Whether or not the SCANDAL hypothesis finds more support, the Tasmanian devil study points to an essential truth. If it spreads like a parasite, and if it drives adaptation like a parasite, it may as well be one.

Bibliography:

1. Metzger MJ, Villalba A, Carballal MJ, et al. Widespread transmission of independent cancer lineages within multiple bivalve species. Nature. 2016;534(7609):705-709. doi:10.1038/nature18599

2. Epstein B, Jones M, Hamede R, et al. Rapid evolutionary response to a transmissible cancer in Tasmanian devils. 2016. doi:10.1038/ncomms12684

3. Panchin AY, Aleoshin V V, Panchin Y V. From tumors to species : a SCANDAL hypothesis. 2019:1-10.

Jabale is a Junior in the School of Life Sciences at IUB majoring in Biochemistry. He is a future scientist who is crazy about everything related to biology, especially genetics.

Cancer: An Unwanted Guest

Jabale Rahmat

Freshman

School of Life Sciences

Independent University, Bangladesh

May 26th, 2017

Lamia, a middle-aged woman, is sitting in the waiting room of a clinic with a receipt in her hand. She is waiting for her number to be called to collect her mammography report. She is watching the preview window which shows the call number for the next patient. When her number comes, she stands up with fear on her face. She moves toward the reception desk and collects her report. She is scanning the report with frightened eyes and praying to God for a negative result for breast cancer.

If just the possibility of cancer can be so frightening, how much more suffering will come from a positive diagnosis?

“Cancer”, the word, carries a lot of weight. The disease, cancer, has an effect on both the person and his or her family. Cancer patients are not only devastated by physical pain, but their mental health also gets affected due to the economic burden that they have to bear. A cancer patient essentially becomes a prisoner from the moment they are diagnosed.

How does cancer develop? Cancer at its root is a genetic disease, caused by mutations after birth that cause abnormal cell division. Cell division is a process by which a single cell multiplies into two. From growth to the replacement of dead cells, cell division plays a vital role in all living organisms, including human beings. When we cut our hair, new hair grows through cell division. Millions of red blood cells die in our bodies every day and new blood cells are generated through cell division.

There are many factors that affect cell division. Cell division is not a random process. When a cell receives a certain signal, the cell divides. Cells in the heart hardly divide unless there is any abrupt change, for example cell death. To compensate for the loss of dead cells, a signal is sent from nearby cells, which in turn triggers a cell to divide and replace the lost cells. Therefore, cell division is a “programmed” process. Unlike healthy cells, cancer cells divide randomly and continuously – i.e. cell division in cancer cells is a broken program.

Experiments have shown that cultured human cells can only grow outside the body if special chemical growth factors (normally produced by human tissues) are added to the nutrient broth. But cancer cells are often able to grow on simple nutrient broth that completely lacks any added growth factors. This suggests that cancer cells manage without the growth factors that are necessary for normal cells to grow inside organs and tissues. Thus, the question arises – how do the cancer cells manage to divide without growth factors?

Probable genesis of cancer. Stanford

The program for cell division is contained within the genetic content of a cell. When a cell reproduces, the contents of that cell reproduce as well. During normal cell division, several genes are involved in making sure that the cell has enough resources to divide into two cells. Genes are made up of DNA. DNA molecules are very inert, that is, they are resistant to many chemical reactions, but they can still get damaged when they come into contact with certain chemicals. We call these chemicals carcinogens. Cigarette smoke is a potent carcinogen that can damage DNA molecules when inhaled. The DNA damage can result in mutations that trigger abnormal cell division by affecting genes that are involved in regulating cell division. This in turn can result in cancer.

The genes which cause cancer when damaged can be characterized as either proto-oncogenes (genes whose activity normally promotes cell division) or tumor suppressor genes (genes that normally prevent cancerous cell division in healthy bodies). I will discuss some examples of these genes below.

Under normal circumstances, proto-oncogenes induce cell division, and then stop. Mutations in proto-oncogenes can transform them into oncogenes that cause continuous cell growth. HER2 is a proto-oncogene that in its mutated, oncogene form gets overexpressed in many types of cancer cells, and makes them hypersensitive to very low levels of growth factors. Growth factors mediate their effect by binding to receptor proteins present on the surface of the cell. When they come into contact with the growth factors, these receptor proteins cause chemical changes inside the cell that trigger cell division. HER2 encodes one such receptor, and overexpression of the gene results in the presence of large amounts of receptors on cancer cell surfaces, which is what makes them hypersensitive to growth factors. This causes the cells to divide uncontrollably. Some mutations in HER2 can also induce cell division without the presence of the growth factors. In other cancers, researchers have seen that cancer cells can start to produce their own growth factors, leading to cancerous cell proliferation. Many oncogenes cause cancer in this manner by reducing the dependency of cancer cells on external growth factors.

Even though our body is constantly exposed to carcinogens, for instance in the form of UV radiation in sunlight, this does not result in cancer in the vast majority of cases. This is because tumor suppressor genes like TP53 can respond to the DNA damage caused by carcinogens and prevent the development of cancer cells. For example, p53, the protein encoded by the TP53 gene, can respond to DNA damage by triggering apoptosis, a form of programmed cell death, and clear tissues of potentially cancerous cells.

But what happens where is a mutation in the TP53 gene itself? This can be caused by DNA damage caused by carcinogens like cigarette smoke. This will impair the gene’s ability to identify and respond to further DNA damage in the future. Thus, the unwanted guest, cancer, can enter. Normally, multiple mutations of the types we discussed need to occur before cancer arises.

Some people may have increased risk for certain forms of cancer due to the presence of some mutation that they inherited from their parents. But it is always true, regardless of whether a patient inherited genetic risk factors from their family, that all forms of cancer are genetic diseases caused by mutations in cellular DNA.

Despite this increased understanding, to this day there is no permanent cure for the disease. Millennia after its discovery and after a century of biomedical research, scientists have made incredible progress in treating cancer, but many forms and stages of cancer remain untreatable. There are also many moments when physicians think that they have cured a cancer patient fully, only to find that a few months later the same patient comes back with a powerful and resistant form of the disease. The disease can be cured but not its successors.

The war against cancer is an ongoing struggle that brings together patients, oncologists, and biomedical researchers. Chemotherapy results in the evolution of resistant cancers, forcing researchers and oncologists to come up with new technologies and strategies. This war is not new, but has been going on for thousands of years. Until scientists can develop reliable permanent cures, the war against cancer will never end, and people like Lamia will have to live with the fear and possible trauma of cancer.

Jabale is a Fresher in the School of Life Sciences at IUB majoring in Biochemistry. He is a future scientist who is crazy about everything related to biology, especially genetics.

Understanding Chemotherapy

Farah Husyn
Senior
School of Life Sciences
Independent University, Bangladesh

March 21st, 2017

Due to advances in technology, early cancer survival rate has doubled in the past 40 years. There are surgeries, radiation treatments and chemotherapies to treat cancer. In order to understand chemotherapy we first need to understand what cancer is. It is a disease which causes the body cells to divide rapidly and uncontrollably. It may start anywhere on the body and spread to other tissues. But all abnormally dividing cells do not lead to cancer and many form completely benign growths and tumours. There are more than 200 different types of cancers.

Though cancer does not have any specific cure, chemotherapy is one of the most common treatments for cancer. In chemotherapy, various anti-cancer drugs are used to treat the disease. Chemotherapy stops or slows down the growth of cancer by specifically targeting rapidly dividing cells. It is a systemic treatment, which means it affects the entire body. This treatment may be given alone or along with other treatments such as radiation and surgery.

The history of chemotherapy is interesting and rather surprising. During World War II mustard gas was used as a chemical weapon. The US army was trying to find a more effective gas to use in their warfare and, ironically, they found the chemicals in mustard gas to work against a type of cancer, saving lives. After being discovered in this manner, chemotherapeutic drugs are now a multibillion-dollar industry.

Cancer survival rates over time. Macmillan

Depending on the type and severity of cancer, the cost of 8 weeks of chemotherapy treatment can range from $100-$30,000 or more. Chemotherapy may completely cure the patient by destroying all cancer cells, or simply prolong their life span for a few more months or years if some cancer cells remain. It can also be co-administered with surgery or radiation to improve the efficacy of these treatments.

Chemotherapy is generally delivered by injecting it inside veins. It can also be taken orally. It is usually a long and continuous process. If the dose of chemotherapy is not too high or complex then patients do not need to be hospitalized and may receive the treatment at home or during visits.

But everyone does not react to chemotherapy the same way. They react differently to chemotherapeutic treatments depending on their type of cancer and personal fitness. Patients need to be fit enough to take the treatment. Before suggesting chemotherapy various organs are checked as chemotherapy puts strain on the body.

There are many side effects of chemotherapy. While destroying the rapidly diving cancerous cells, chemotherapy also hampers healthy cells of the body that happen to be dividing rapidly, such as hair cells, resulting in hair loss. Immune cells, our body’s defenses against pathogens, are generated from rapidly dividing blood cells in the bone marrow. Chemotherapy therefore also results in immune suppression, increasing susceptibility to infectious diseases. Other common side effects include pain, diarrhea, nausea and vomiting, and loss of appetite. The side effects can be treated separately and this form of treatment is known as palliative care. There is also a risk of developing a different type of cancer for cancer survivors after using chemotherapy. Usually the side effects disappear after the treatment is finished but some might be long lasting.

Many people think that chemotherapy causes a lot of harm without being effective at treating cancer. But there are two very important things that we need to keep in mind. Firstly, cancer does not have any definitive cure till date. Secondly, there are hundreds of types of cancers. Each type reacts to treatments differently. Chemotherapy happens to employ a mechanism that is effective in most cases, but may fail due to other factors. Researchers are still trying to find more effective ways of treating and curing cancer.

Farah Husyn is a senior year student at SLS, and has already started to miss IUB. Her one and only passion is reading books. She wishes to be a millionaire in the not too far future.

The BRCA1 Gene: Understanding Why Some Women Opt for Mastectomy

Fabiha Atiq
Freshman
School of Life Sciences
Independent University, Bangladesh

March 23rd, 2017

Ever wonder why people say your nose looks like your mom’s nose or that your eyes remind them of your dad? The answer to your question is DNA. DNA (deoxyribonuleic acid) determines characteristics that are passed from parents to children, such as blood type, hair colour, eye colour, etc.

Genes are made of DNA and they contain information to build and manage cells (smallest unit of life) in the body. The BRCA1 gene is a human tumor-suppressor gene, found in all human beings. BRCA1 stands for BReast CAncer susceptibility gene1.

Tumor-suppressor genes are genes that normally prevent cancer by controlling cell division. When they do not work properly cells start dividing rapidly and uncontrollably, which can lead to cancer. Mutations are changes in the genetic sequences that can lead to changes in their function. BRCA1 is a tumor suppressor gene; when it undergoes certain mutations it leads to an elevated risk for breast cancer.

When women are diagnosed with breast cancer, doctors may suggest a lumpectomy or surgical removal of the affected part of the breast. In extreme cases, a mastectomy, which is the surgical removal of the complete breast/breasts, may also be recommended. The purpose of these procedures is to treat and preemptively reduce chances of recurrence of breast cancer by surgically removing cancerous tissues, along with adjacent healthy tissue in the surrounding area.

The mutated BRCA1 gene increases the likelihood of developing breast cancer by 55% or more. While regular monitoring after detection of the mutated BRCA1 could effectively deal with the risk if cancer does arise, there have been a few cases of women opting for preventative mastectomy to avoid developing breast cancer in the future. Often, women who opt for preventative mastectomies are the ones who have a history of breast cancer in their family and are carriers of this mutation.



A famous case of preventative mastectomy that circulated on the internet was that of celebrity Angelina Jolie. She had both of her breasts surgically removed because she carried the mutated BRCA1 gene and was at high risk of getting cancer. Her mother, grandmother and aunt had all died from cancer. By opting for a preventative mastectomy, she showed women all over the world that this procedure can be a normal part of women's health, instead of a source of shame or embarrassment.

To put the public health burden of breast cancer into perspective, 508,000 women died from breast cancer in 2011 alone worldwide.  Once they turn 40, all women should get themselves checked for breast cancer, or at least start thinking about it, according to recommendations from the American Cancer Society.

“Knowing it exists isn’t enough. Get informed. Pass it on.”– Breast Cancer Awareness Slogan.

Fabiha is in her first year of IUB, and aspires to be a forensic scientist. She is a bookworm, a shutterbug, and loves to write.