Thinking Your Way Through a Labyrinth of Contemporary Issues
The short answer is yes. But that wouldn’t be much of an article now would it? I want to discuss what I think about the state of cancer treatment at the moment and its future.
Cancer has been a personal interest of mine and I pursued those interests in university undertaking two cancer-related lab projects. Cancer is a very interesting subject and there is a lot of research being undertaken to understand the molecular biology of cancer and how to treat it and there has been quite a lot of success in understanding certain cancers and developing successful treatments for them.
Ever since the introduction of chemotherapy and various other therapies there have been cases of patients being successfully treated and are still alive now, and for certain cancers which have effective treatments there are many survivors. But the common trend is the majority of the cancer gets destroyed causing symptoms to disappear until the few cancer cells that are left (which are treatment-resistant) have time to divide and form new tumours and the patient becomes sick again and eventually dies.
There is a common notion (among non-cancer researchers) that we are waiting for a singular cure for all cancers. Granted that would be amazing and whichever company finds it will quickly bury it and kill the recipe with fire! (Pharmaceuticals don’t actually want or care about finding a cure or short-term treatments as they think it won’t make them a lot of money, which is of course stupid, because they are trading a massive boost to their reputation and prestige for greed). Anyway, fundamentally pharmaceuticals are trying to develop treatments to prolong a patient’s life which naturally coincides with treatments that kill the cancer and stops its growth. Each cancer type (originating from a particular tissue in the body) is basically unique (as well as each individual’s cancer). So finding one treatment that will work for all or most cancers is a bit farfetched, just like you wouldn’t use heart medication to treat diseased kidneys and vice versa. So each cancer type has its own disease progression and requires its own strategy for treatment, and this can be easier for certain cancers than others.
In the past 30 years great strides have been made in the biological understanding of certain cancers and effective treatments such as for breast cancer whereas for certain cancers our knowledge is very basic such as pancreatic cancer.
Below is a short list of some common cancers and 5-year survival rates (the number of patients alive 5 years after diagnosis) according to Cancer Research UK. US statistics are quite similar.
|Cancer||5-year survival (%)|
So cancer is not the death sentence it used to be thirty years ago though for certain ones like pancreatic cancer, you basically have a year to live once it has been diagnosed. These massive differences in survival for different cancers are due to how much knowledge we have of the biology of these cancers and the development of targeted therapy based on biological information. A great example is the finding of a subtype of breast cancer which is oestrogen-dependent (i.e. the cancer needs oestrogen hormone to grow and survive) and then the development of a drug (Tamoxifen) which binds to the oestrogen receptor on the cancer cells and stops oestrogen from binding with the receptor. This coupled with chemotherapy or radiotherapy became a very effective treatment for these women and they tended to survive. Whereas, knowledge of pancreatic cancer and its progression has remained very rudimentary until recently, and survival hasn’t changed for the past 50 years.
Here’s what we do know about the general way cancer develops and progresses and then becomes treatment resistant: in one cell somewhere in the body a mutation occurs in a gene that codes for a protein that has a role in protecting the DNA and/or role in cell division. This mutation occurs for a multitude of reasons including mutagens like carcinogens and radiation, inherited defects in those genes as well as chronic inflammation which creates an environment rich in radicals and promoting cell division (thereby increasing chances of mutations occurring). The loss of control over DNA integrity and division then leads to more mutations occurring until the cell loses all control over its cell division. It is at this point that a tumour will grow into a large lump known as the primary tumour. A cancer caught at this stage is at its most treatable and various chemotherapy treatments can be very effective as well as surgery. If left too late then some of the cells of the tumour mass would have gathered enough mutations to allow it to survive in the bloodstream and lodge in other tissues of the body leading to the development of secondary tumours also known as metastases. This is what tends to kill the patient as these metastases lead to organ failures. Drug resistance in cancers arises due to the selection pressure caused by the drugs. The drugs kill the majority of the primary tumour but some cells have acquired mutations that allow it in some way to escape the effects of the drugs (for example a protein pump becomes non-functional and therefore the cell can’t pump the drug inside so the drug can’t carry out its effect).
A big part of cancer research is devoted to understanding the biology of the cancer, which includes characterising all the genetic and molecular defects, which genes are switched on and/or off and which contribute to growth and metastasis (spreading). Finding essential molecular pathways shows us which ones the cancer cells are depending on and therefore its vulnerabilities. Using these vulnerabilities drugs can be synthesised that specifically target proteins we want to target, which leads to possible drug candidates. That’s just the beginning and possibly is very easy with the use of computer software today. The thing that takes a while is finding one that is therapeutic and non-toxic. Various characteristics of the drug have to be tested and tweaked so that they are non-toxic, stay in the body long enough to carry out their effects, specifically bind with our targets, and have a large enough effect at reasonable doses.
For many cancers the go to treatment is chemotherapy and radiotherapy which essentially aim to kill the cancer cells by poisoning them and generally work by damaging the DNA or interfering with DNA replication to an extent that the cells die. The strategy of these treatments depends on cells that divide and grow fast such as cancer but this applies to other fast-growing tissues such as hair follicles, skin, and immune cells hence patients experience hair loss, pale weak skin and low immunity.
However, more research is being done in developing targeted therapies such as antibodies, and drugs to boost immune system attack against cancers, viruses as well as other methods such as the development of nanobots which could in the future be used to kill cancer cells.
Below are five cancers and the exciting new therapies that are either under clinical trial or have promising drug targets as well as state of current treatments.
1. Brain cancers
• Currently brain tumours are treated by temozolamide, radiation and surgery either all together or combinations of each
• There are various types of brain cancers such as glioblastomas and gliomas. There is research being undertaken to test a dye called 5-ALA (or Gliolan) that makes the tumour glow red under ultraviolet helping the surgeon find the tumours. After the surgery a chemotherapy implant called a Gliadel wafer will be implanted at the surgery site to kill any remaining cancer cells.
• Various radiation therapies are being researched for brain tumours such as proton therapy and boron neutron capture therapy. Proton therapy involves shooting protons precisely at the target tissue and can be a very effective treatment as was shown for Ashya King. Unfortunately proton therapy centres in the UK only treat cancers in the eye, but proton centres in the US and Europe can treat brain tumours.
• Drugs that target the cancer’s growth are being researched such as tyrosine kinase inhibitors and PARP inhibitors. Also an antibody has been developed called bevacizumab (Avastin) which has been shown to delay glioblastoma relapse.
2. Breast cancer
• Breast cancers tend to be hormone dependent and there various subtypes to see if the cancer is positive for oestrogen receptor, progesterone receptor or HER2 receptor or a combination of these. If the breast tumour is found to positive for these receptors, then these receptors can be blocked with drugs. The most untreatable breast cancers are the triple negative ones which don’t have any of the aforementioned receptors. Various strategies are being researched to treat triple negative breast cancers such as PARP inhibitors
• Research is also being done to determine if genetic testing prior to treatment can help determine the best treatment plan for patients with breast cancer. This is also something that will hopefully become more prominent in future years when genetic testing becomes more widespread and cheap.
3. Head and neck cancers
• These are cancers that originate in the nose, mouth and throat regions. Currently head and neck cancers (HNC) can be treated with cisplatin, radiation (X-rays) and surgery.
• There is research being done in targeting the Fanconi Anaemia (FA) pathway in HNC to make these cancers susceptible to cisplatin treatment. Cisplatin is a platinum-based chemotherapy treatment which essentially links the two strands of DNA together making the cell unable to replicate. The FA pathway can repair these links and the cell survives cisplatin treatment. If the FA pathway can be knocked out, the cancer cell won’t be able to repair the DNA damage caused by cisplatin treatment.
• An innovative new treatment is being research which combines laser treatment with chemotherapy. The treatment involves giving the patient two drugs: Amphinex (which makes the body more sensitive to light) and bleomycin (a DNA damaging agent). Then lasers are shone directly on the tumour or through optic fibers. The laser activates Amphinex which then helps bleomycin to enter the cells and kill them.
4. Lung Cancer
• There are two broad types of lung cancer: small cell lung cancer and non-small cell lung cancer. Treatment for small cell lung cancer involves chemotherapy with radiation therapy on the lungs and brain if the cancer has metastasised there. Common treatments used are cisplatin or gemcitabine with carboplatin. Non-small cell lung cancer can be treated with a combination of surgery, chemotherapy and radiotherapy.
• Some non-small cell lung cancers (10-15%) are positive for epidermal growth factor receptors (EGFR), i.e. these cancers require EGF for growth and survival and can be treated by blocking the receptors with an antibody called Erlotinib (Tarceva). Various antibody drugs have been developed to treat various advanced lung cancer cases.
• Research is being carried out to study the faulty genes in lung cancer to determine the best treatments for the patient. New antibodies are being developed to treat certain advanced forms of lung. For example, Crizotinib can bind and block the effects of a protein called ALK (which plays a role in survival) and is overactive in certain lung cancers.
5. Pancreatic cancer
• Pancreatic cancer treatment is quite dismal (compared to other cancers). Pancreatic cancer is usually treated with gemcitabine but chemotherapy treatment is very ineffective. This is because with pancreatic cancer (specifically pancreatic ductal adenocarcinomas) there is a mass of tissue surrounding the tumour (known as the stroma). The stroma contains a variety of cells such as immune cells (macrophages, dendritic cells, helper T cells), fibroblasts, acinar cells amongst others and it is thought (with evidence of course) that the stroma mostly serves to promote tumour growth and survival. The tumour subverts macrophages and other cells to make them secrete factors to create a microenvironment that promotes tumour growth. Also the immune system is suppressed by the macrophages so that the tumour doesn’t get attacked by T cells.
• A lot of the details of how the tumour interacts with the immune system are still being worked out, but targeting macrophages and activating cytotoxic T cells is a very attractive strategy in treating pancreatic ductal adenocarcinomas.
• A cocktail of chemotherapy drugs called FOLFIRINOX has been shown to provide the best survival benefit (though this only increased survival by a few months). Currently pancreatic cancer patients survive for about 18 months with current treatment. A more appealing strategy is to target the stroma which the tumour depends on and various therapies that target the stroma are being tested.
Obviously there is more research than what I have alluded to here as thousands of research papers are being published every day which is very heartening.
In general the earlier the stage the cancer is in, the easier it is to treat because it is more vulnerable to treatment and it hasn’t spread much to the rest of the body so is easier to eradicate. There is a great emphasis in research in earlier detection strategies for cancer. The high survival rate of breast cancer patients is due to regular screening for lumps leading to early detection of breast cancer which can be treated by surgery and a bit of chemo or radiotherapy.
The body has many defence mechanisms against the development of cancer (in fact cancer cells do arise in most of us from time to time but the cells either kill themselves or get killed by the immune system). Many cancers have long incubation periods where a small growth develops and then over many years accumulates mutations until full-blown cancer develops (such as in the case of lung cancer, or polyps in colon which lead to colon cancer). Although you can inherit a predisposition to developing cancer by inheriting faulty genes, many cancers develop due to lifestyle choices. Smoking, alcohol and poor diet (rich in fats and salt) can lead to cancer. With smoking it is basically a direct cause: some smoke particles can damage the DNA of some lung cells. This leads to mutations and also causes inflammation. The inflammation nurtures a state of growth and replication so mutations accumulate. After about 30 years a smoker can develop lung cancer. Alcohol and obesity leads to cancer because they also promote chronic inflammation which is an important factor in the development of many cancers. Eating fatty foods (like pizza) stimulates the colon cells to divide faster, leading to an increased chance in mutations occurring, and could ultimately lead to colon cancer.
Reducing inflammation in the body by leading a healthy lifestyle will go a long way in reducing the risk of developing cancers in your old age (which is when most cancers are diagnosed).
Western medicine has a lot of promise in providing treatments that can prolong lives and at best can even cure cancer sometimes in some patients. But that is not to say it is not possible to be treated in other ways.
Plants contain many organic compounds which can bind to certain proteins in our bodies. For example before the commercialisation of aspirin, willow bark was brewed as a tea to relieve pain. The active ingredient salicylic acid would be concentrated in the tea and get into the body when we drink it. So although western medicine is looking to design inhibitors against various proteins in the cancers, there is undoubtedly natural molecules that can antagonise the same proteins which could be found in plants. This is why herbal remedies are a great alternative if you know what herbs to use. Also in my opinion herbal remedies tend to be more balanced as you are not only getting the active ingredient but a host of other chemicals which have synergistic effects and limit side effects, whereas giving the active ingredient by itself would mean taking other drugs to counter the side effects of the drug.
Cancer research is at a furious pace to fill in the many gaps in our knowledge of cancer and we are making great strides in various common cancers such as breast cancer. Cancers are generally treated with a mixture of surgery, chemotherapy and radiotherapy, but many biological therapies are being developed that specifically target the cancer to stop its growth and kill it such as immunotherapy which uses antibodies to block essential proteins for the cancer. Innovative therapies are being tested and soon these will be on the market in a matter of a decade or two. Greater use of genetic testing will allow better treatment plans to be drawn up and so therapy can be patient-specific. Hopefully in the future there will be a greater emphasis on therapies that specifically target cancer cells and leave the rest of the body alone.
Mohammed Wilkinson, (2015)
If you have any questions or thoughts feel free to post them in the comments.