Cancer and Precision Medicine

Cancer and Precision Medicine

By Lee Yeuan Ting and Dr. Oon Chern Ein

At a Glance:

Cancer is a deadly disease with a high mortality rate. Cancer refers to the abnormal growth of cells, which can grow to be either benign (non-invasive) or malignant (invasive). There are many options available for cancer treatment including surgery, radiotherapy and chemotherapy. However, patients may not respond in the same way to fully benefit from these treatments. With the increasing wealth of genomic knowledge, more strategies can be explored to improve treatment outcomes, and one of them is precision medicine.

How does cancer develop?

Cancer develops when one or more cells undergoes DNA damage that fails to be detected by the body. The unrepaired DNA damage may cause gene mutation that leads to malfunction in cellular events affecting cell growth, division and death. In normal cells, cell proliferation and cell death are controlled genes that either favour or stop cell division. However, mutation resulting from DNA damage allows the cancer cells to survive and proliferate either by disregarding signals that halt cell division or by triggering the cells’ ability to produce growth factors which promote cell survival, or both (Figure 1).

Figure 1: Cellular events associated with DNA damage in normal and cancerous cells. A) Cellular repair mechanisms in normal cells are highly regulated by the body to correct genetic abnormalities while B) cancerous cells are flawed in their repair mechanisms, and thus divide uncontrollably, leading to tumour formation.

Cancer can be caused by both intrinsic and extrinsic factors. Intrinsic factors refer to genes inherited from either parent that predisposes an individual to develop cancer, or gene mutation that occurs spontaneously within the individual. In the case of inheritance, the probability for an individual to develop cancer increases if there is a history of familial cancer. DNA damage can also be caused by extrinsic factors which encompasses environmental and individual lifestyle factors. According to the World Health Organisation (WHO), environmental factors such as ionising and non-ionising radiation, alcohol use, smoking tobacco and a sedentary lifestyle may contribute to higher risk factors for developing cancer.

What is precision medicine?

Besides radiotherapy and surgery, chemotherapy is the most common strategy for cancer treatment. It involves the use of cytotoxic or cytostatic drugs to kill cancerous cells. However chemotherapeutic drugs are known to also affect normal cells as they indiscriminately kill rapidly dividing cells such as cells in the nails, blood, stomach lining and hair. The chemotherapeutic agents are mostly cytotoxic, leading to unwanted side effects in patients. The common toxicity or side effects include fatigue, nausea, vomiting, hair loss, mouth and throat sores, diarrhoea, blood disorders and appetite loss2. In addition, the current drugs are prescribed as “one size fit all”, and thus are less effective for everyone as some patients may not respond to these treatments. As such, precision medicine holds a big promise in cancer treatment.

Precision medicine, also known as personalised medicine or individual medicine, is an emerging approach for disease treatment and prevention. It targets different patients based on their unique circumstances by taking into account their genetic profile and environment and lifestyle factors. The genetic variations in each individual may affect how a patient responds to a certain drug. Single nucleotide polymorphism (SNP) refers to the difference in a single nucleotide of DNA that contributes to genetic variation in each individual. SNP may cause some individuals who carry a particular variation of a gene to be more susceptible to a certain cancer type or may even protect them from the disease. Environmental factors and individual lifestyle have been shown to influence gene expression and how an individual responds to treatments. SNPs are useful to predict how an individual may respond to certain drugs, environmental factors and to assess their risk of developing particular diseases. By combining the information yielded by an individual’s SNPs with precision medicine, medical treatments may be precisely tailored to ensure that the most effective drugs and suitable doses are administered to the patients.

The current advance in biotechnology and the completion of the Human Genome Project have paved the way for the efficient application of precision medicine. New treatments are customised for every patient by sequencing the genetic profile of an individual’s tumour. Cancer is mostly attributed to severely irreversible gene mutation that may vary in different patients according to cancer type, stage or location. Precision medicine can target and track these mutations through initial sequencing of the genome in the tumour sample obtained from each patient (Figure 2). Identification of the cancer-driving mutated genes will then allow doctors to prescribe drugs that specifically target cancerous cells without harming other non-cancerous cells in the body.

Figure 2: Schematic flow of precision medicine. Precision medicine allows patients to be treated by tailoring therapies according to their genetic make-up.

In short, precision medicine involves studying and understanding how an individual’s health is influenced by the interaction between environmental factors and genetic variations. Through these information, healthcare providers can better predict a patient’s response to the drugs. This allows the doctor to give the right treatment at the right time to the right patient for better treatment outcomes.

References:

  1. World Health Organisation. (2015). Cancer. Retrieved from http://www.who.int/mediacentre/factsheets/fs297/en/
  1. Net Editorial Board. (2015). Side Effects of Chemotherapy. Retrieved from http://www.cancer.net/navigating-cancer-care/how-cancer-treated/chemotherapy/side-effects-chemotherapy

About the Authors:

Dr Oon Chern Ein completed her BSc (1st Class Hons) in Biotechnology at Universiti Kebangsaan Malaysia before securing a scholarship from the Ministry of Higher Education Malaysia to further her doctorate studies in Medical Oncology in University of Oxford, United Kingdom. She then trained at Karolinska Institutet, Sweden as a postdoctoral fellow before returning to Malaysia as a lecturer at Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia. In 2014, she won the Exiqon Young Scientist Award- South East Asia and was the sole recipient of the Ranjeet Bhagwan Singh Medical Research Trust Fund. Chern was selected by the Council for the Lindau Nobel Laureate Meetings to participate in the 65th Lindau Nobel Laureate Meeting in Germany in 2015. She continues to receive numerous awards for her work on novel molecular therapeutics in cancer including the prestigious L’Oreal-UNESCO for Women in Science National Fellowship in 2015, the Union for International Cancer Control Fellowship and MAKNA Cancer Research Award in 2016. Check out Dr Oon’s Scientific Malaysian profile at  http://www.scientificmalaysian.com/members/chernein/

Lee Yeuan Ting graduated with a first class in Bachelor of Science (Honours) in Molecular and Cell Biology, Universiti Putra Malaysia. She is now pursuing her MSc at INFORMM, Universiti Sains Malaysia. Her research project is on preclinical toxicology and mutagenicity study of a novel anti-cancer agent. Check out Yeaun Ting’s Scientific Malaysian profile at http://www.scientificmalaysian.com/members/leeyeuanting/