Introduction– Precision cancer medicine involves the personalised treatment of cancer. It relies on specific molecular changes which cause the disease of the particular individual patient. This differs from the traditional treatment where different patients are treated using the same treatment. It is now well-understood that cancer is essentially a genetic disease which can be either hereditary or acquired throughout the lifetime. Indeed, cancer initiates when genome undergoes mutations, which result in the oncogenes (a gene that has the potential to cause cancer) coding for the uncontrollable cells division leading to cancer metastasis.In the precision cancer medicine, we focus on understanding key mutations that cause cancer in each independent patient. This focused understanding help treat each patient more effectively, as we target the specific aberrations in the genome which is achieved through molecular diagnostics.
History – The concepts of biology initially emerged in the early 19th century after the significant advancements made in the fields of chemistry and physics. Then came “molecular biology”, a term coined in 1938 by Warren Weaver (an American scientist) , who was among the first to recognize the importance of sciences in understanding the core mechanisms of life. In 1953, the discovery of DNA structure and replication by James Watson and Francis Crick [2,3], cemented molecular biology as a coherent scientific discipline. However, despite multiple investigations into cancer, molecular diagnostics of cancer did not rise into prominence until decades later. Molecular diagnostics involves the application of molecular biology to medical testing as well as the analysis of biomarkers in either DNA, RNA, or protein. It arose in the 1980s after a prenatal genetic test for Thalassemia . It was only a decade later, when the precision cancer medicine emerged, following two molecule-targeted therapies treating breast cancer and leukemia, respectively .
How does it work? – Initially, precision cancer medicine mainly involved the use of targeted therapies such as vascular endothelial growth factor (VEGF) inhibitors or BCR/ABL inhibitors. Example of these inhibitors include bevacizumab and imatinib . However, the use of these therapies has been largely discontinued, which has led to the reliance on data from the analyses of biomarkers in order to determine which therapies to select. One example is the use of adjuvant chemotherapy, which is influenced by the results of genomic testing such as the Oncotype DX panel (tumor profiling test) in women with breast cancer . Despite the conventional cancer taxonomy relying on the site of origin of tumours and their histopathology (the changes in tissue that the disease causes), precision cancer medicine is focusing on specific biomarkers that are acquired from biopsies. These now include liquid biopsies (using bodily-fluids) which have been shown to contain nucleic acids derived from tumours as well as biomarker-containing circulating tumour cells (CTCs).
Biomarkers can serve several purposes. For example, predictive biomarkers help show what is most likely to happen in response to a certain type of treatment. A common example of this would be the EMFL4-ALK fusion gene which can be treated with ALK-targeted inhibitors in lung adenocarcinomas (a type of lung cancer originating in glandular cells). Diagnostic biomarkers enable the differentiation of different cancer and tumour types. For example, the BRAF V600E mutation can be used to differentiate hairy cell leukemia (HCL) from different morphologically similar leukemias and lymphomas. Prognostic biomarkers indicate the most likely course the disease will take, allowing us to form more tailored treatment strategies for each patient in question. For example, mutations in the ASXL1 and EZH2 genes in myelodysplastic syndromes (MDSs) which are cancers preventing blood cells in the bone marrow from maturing .
Precision cancer medicine has made leaps in progress as a novel approach to cancer treatment. Because of the subtly heterogenous nature of tumours, molecular profiling has played a crucial role in understanding the role genomics in the development of different cancers. As we continue to accumulate more data containing the various cancer driver genes, we may improve the outcome for many patients who are still in a dark period of uncertainty, and maybe soon give more hope.
COPYRIGHT: This article is the property of We Speak Science, a non-profit institution co-founded by Dr. Detina Zalli and Dr. Argita Zalli. The article is written by Albin Shaqiri, Queen Mary University of London, UK.
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