What is the problem with the current paradigm of medicine?
If you’re sick, you go see a doctor and the doctor prescribes you some medicine. Does the doctor know whether this medicine is going to help you get better? The answer is probably not. What they do know is that during phase III clinical trials, 5 out of every 10 people with symptoms similar to you benefited from the drug and got better.This could be as low as 1/10 or as high as 9/10. Fundamentally the way the drug is being prescribed has little to do with you. If we assume you haven’t taken this drug before, the doctor does not know how you specifically will react. They know how the general population will react- whether this is 5/10, 1/10, or 9/10 recovering- but not you specifically. The way we approach medicine is aone-size-fits-all approach. You and your friend could be given the exact same drug (since you have the same disease) even though you’re different people. You could have no reaction to the drug while your friend could recover from the drug. Alternatively, you could suffer hair loss, vomiting or even die from the drug while your friend could experience none of these. If you look at the image, the doctor has no idea which subset of the population you will be part of- effect, no effect or adverse effects.
According to the BMJ, 1/3 medical treatments have a proven benefit to patients (2/10 for cancer drugs) and 7000 people died from medical drugs in the US in 2018 alone.
What if we could prescribe drugs knowing how someone will react to the drug. This is what personalized medicine hopes to achieve. Generally, it is a better way of treating a disease, where the diagnosis and treatment is based on a patient’s genome rather than on clinical trials. Hopefully this would maximise efficacy and minimise side effects of a drug. As Hippocrates said ‘it is more important to know what sort of person the disease has, than to know what sort of disease the person has.’
Why is cancer?
It is one of the main causes of deaths in the US with 600,00 cancer-related deaths in 2018 in the US alone. Half of men will have cancer with 1/4 dying from it. It is 1/3 and 1/5 for women.
Generally cancer is caused by an accumulation of cell mutations causing the cell to divide uncontrollably, resulting in a tumour. The difficulty with treating cancer is that it the type and cause of cancer varies greatly from person to person. Cancer is not a single disease but rather a group of over 100 diseases, caused by different genetic and environmental factors and the differing physiologies of people and their cancers makes it very impractical to use the ‘one size fits all’ approach to cancer treatment.
A more precise way is required to screen for and treat the disease.
What is Personalized Medicine?
https://audiotech.com/trends-magazine/building-the-foundation-for-personalized-medicine/
Essentially, the idea is that by looking at a patient’s genome we can prescribe a drug/ dose of radiation that is personalized to them and therefore would have the greatest effect on them with minimal side effects.
Chemotherapy
During WWI, a key weapon used on both sides was mustard gas. Those who were exposed to it struggled to breathe, struggled to see and blisters appeared on the skin. This was a deadly weapon hence why scientists worked throughout the war to develop an antidote for the gas.
What mustard gas would do was that it would irreversibly damage the bone marrow of affected soldiers. This stops the stem cells in bone marrow from dividing into blood cells. Now cancer cells are very similar to these stem cells (divide and replicate very quickly) and one of the questions that was asked was whether one of the atrocities of war could be used to fight cancer. Researchers during this period experimented with different compounds from mustard gas and eventually developed a substance that damaged the DNA of dividing cells, which leads to cell death unless the damage is repaired. Since cancer cells divide very quickly they take up a lot of this substance, compared to other cells which have the time to fix the DNA. Therefore, hopefully cancer cells start to die off. Through much trial and error, by the end of the war, the first chemotherapy drug was developed.
Essentially, chemotherapy is the usage of drugs to kill cancer cells and is one of the main ways of treating cancer even though it is only effective 11% (take figures with a pinch of salt) of the time. The problem with chemotherapy is that our genes often have a significant impact on the effects drugs have on our body. A drug could have absolutely no effect on you while helping someone a lot older and a lot less fit recover. This is due to your genes.
A study showed that people with the protein ERCC1 did not benefit from chemotherapy since this protein was suspected to help repair the DNA of cancer cells/ 44% of the population have this protein. This is a problem since chemotherapy is accompanied by a wealth of side effects such as hair loss, organ failure and even second cancers. So why are we given people chemotherapy, putting them at risk of the side effects, while knowing there is only an 11% chance of the drug benefiting them (again this is not always the case, some form of personalized medicine is normally used.) A more productive way to use chemotherapy is to target those who benefit and leave out those who will not.
Pharmacogenomics
by John Lynn https://www.healthcareittoday.com/2015/10/16/ehr-cartoons-fun-friday/
Pharmacogenomics is the study of how a patient’s genes will influence their reaction to certain drugs and this is very important in precision chemotherapy. With pharmacogenetics we can determine whether a certain drug will benefit a patient and the extent of the side effects the will receive.
A biomarker is defined to be a genetic or genomic marker that is associated with drug response and certain biomarkers can be used to determine patients who are of high risk to cancer. Others can be used as targets for specific drugs.
In 2013, Angelina Jolie underwent a double mastectomy, an invasive surgical procedure to remove her breasts. In 2015 she had her ovaries and fallopian tubes removed. Why would she undergo major surgery which would naturally result in damaging psychological, physiological and emotional effects? She did this because of pharmacogenomics She did this having learnt that she had an 87% risk of developing breast cancer and 50% risk of developing ovarian cancer. From genetic testing she found she had a mutated BRCA1 gene which she inherited from her mother who had breast cancer and died from ovarian cancer. Due to refined molecular diagnostics and advances in genome sequencing we can predict the risk someone has of developing cancer by looking at genetic mutations and we can later tailor treatments that target these mutations.
Radiotherapy and Personalized Radiotherapy
Radiotherapy has similar problems to chemotherapy. For a subset for a population, radiotherapy is effective but it is not for the rest. Instead of using drugs to kill cancer cells, it involves using high doses of radiation. Side effects can range of minor to life threatening, lasting weeks to a lifetime- eg hair loss, hormone deficiencies and even death.
Like chemotherapy, our genes affect how we react to radiation. This is called radiosensitivity. Radiotherapy could be more effective if we can find a correlation between a person’s genome and radiation sensitivity to find the ideal dose of radiation to yield the greatest benefits but also to minimise side effects. This is called radiogenomics. The idea of this is that by using a patient’s genome we can predict their radiosensitivity, thus limiting side effects and maximising benefits.
Precision chemotherapy and radiotherapy are both more effective ways of treating cancer but the question is how viable is it for them to become widely used.
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