Science Club: Personalized Medicine- part 2

What is Personalized Medicine?

Credit to Trends Magazine: https://audiotech.com/trends-magazine/building-the-foundation-for-personalized-medicine/

Personalized medicine can be argued to have the greatest potential to be the greatest healthcare advancement in recent years. I certainly argued that it was in the interview question what do you think is the greatest scientific advancement in the past decade. 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. 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 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

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 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.