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✍️Madeline Park | MBiol Student at University of Leeds & NHS Lab Assistant in Haematology
What Causes Cancer? 📚
Cells are constantly dividing in our body, and our DNA acts as the blueprint to ensure that when cells divide, they are genetically identical to each other.
However, when changes in our DNA occur, called mutations, dividing cells are no longer identical and so become abnormal. An accumulation of abnormal cells forms a cancerous tumour . Eventually, individual cells can break away from the main tumour and travel around in the bloodstream setting up secondary tumours in other main organs such as the lungs and brain.
What are the Genetic Causes of Cancer? 🧬
DNA is a molecule made up of two intertwining strands called the DNA double helix.
Sometimes the DNA can become sliced in half. This results in double strand breaks and subsequently changes to the DNA. Double strand breaks can form as a result of exposure to X-rays or due to exposure from chemcials in cigeratte smoke. Double strand breaks can also occur spontaneously with no connection to any environmental factors.
What is DNA repair? 🛠️
DNA damage is very common in human genetics with around 50 double strand breaks forming every day in each cell.
The body has therefore developed mechanisms to effectively repair DNA damage and prevent the formation of abnormal cells and subsequent tumours. There are two main repair processes for double strand breaks. One is a more accurate process initated by a molecule called BRCA1. The other is a less accurate but faster pathway initatied by PARP molecules.
What Causes Heritable Breast Cancer? 👪
Everyone carries a BRCA1 gene however mutations in the BRCA1 gene have been associated with the development of breast cancer since 1994 .
Studies of families with mutations in the BRCA1 gene find that loss of the BRCA1 gene is linked to an earlier onset and a 50 to 80% increased risk of developing breast cancer. One of the main hypotheses for this association is the inability of breast cells to repair broken DNA using the error free BRCA1 process. Overtime, breast cells then acquire more mutations and cells become abnormal resulting in the formation of tumours. However it is still unclear why BRCA1 mutations are specifically linked to cancers in breast and ovarian tissue and not other cancers as well.
How can PARP inhibitors target BRCA1 mutant cells? 🎯
Cells carrying BRCA1 mutations are only able to repair DNA damage via the less accurate DNA repair pathway initiated by PARP.
Researcher Steve Jackson, discovered that by preventing this repair pathway with the drug Olapriab (which stops PARP proteins working), only BRCA1 mutant cells are targeted and killed. This is because mutant cells cannot repair DNA as the BRCA1 is mutated, and the PARP molecules are blocked by the drug. This means the the cancer cells cannot divide, leading to their death. Normal cells can still use the BRCA1 error free process to stop DNA damage. Olaparib treatment then specifically only targets BRCA1 mutant breast cancer cells. In March 2022 Olaparib became approved as a treatment for breast and ovarian cancers associated with loss of the BRCA1 gene.
What Comes Next? 🔮
The use of Olaparib in breast cancer treatment signals the beginning of smart and personalised medicines to improve cancer treatment for patients.
It is hoped with advances in gene technology, more drugs can be harnessed to offer less invasive and more effective treatments for cancer.
Edited by: Olivia Laughton | Content Editor | BSc Microbiology, University of Leeds
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