Towards personalized systemic anti-cancer therapies (SACTs)
Frederick Challacombe
Introduction
Cancer is a group of diseases characterized by uncontrolled growth and division of cells; it is also the second most common cause of death after cardiovascular disease. 1 These abnormal cells can spread directly into surrounding tissues or metastasize to distant sites via the lymphatic systems, across a body cavity through fluid (trans coelomic) or via the blood which causes specific symptoms in the new site, or general symptoms such as weight loss, malaise and ultimately leads to death. Cancers develop in several ways which can be related to DNA damage, mutations in the DNA or loss of function of the regulatory and repressor systems within the cell cycle. It is important to note, however, that not all tumours are cancerous as some are benign, meaning that they do not spread around the body. These benign tumours can still be dangerous and cause symptoms if they develop in sensitive areas of the body such as the brain, prostate or uterus. If a cancer is localized at presentation it can be treated directly with modalities such as radiotherapy, surgery or a combination of the two. However, if the cancer has metastasized then a systemic treatment is necessary. Systemic treatments comprise drugs/chemicals that are spread throughout the body to treat cancer cell wherever they may be. These include hormonal therapy, chemotherapy, targeted drugs and immunotherapy and they come under the broad heading of systemic anti-cancer treatment (SACTs). Traditionally over the last decades, all patients with the same type of cancer would receive the same treatment regime. However, recent research has enabled the discovery of specific sub-types of cancer, meaning that an individualized approach is now available for many patients.
Overview
Chemotherapy works by destroying or slowing the growth of cancer cells which normally enlarge and divide more rapidly than other cells. The main side effect of this is that this general chemotherapy also destroys other rapidly dividing normal cells in the body such as cells in the digestive tract, hair follicles and blood cells forming in the bone marrow. Therefore the aim of modern SACT is a more targeted approach in which normal tissues are not affected and the side effects such as fatigue, mouth ulceration and anaemia are reduced. 2 Different cancer subtypes have different genetic mutations in the DNA of their cells. A biopsy of the cancerous tissue, either in the primary or metastasis, can enable oncologists
1 Leading causes of death. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Consulted 22/08/23. 2 Possible side effects of chemotherapy https://training.seer.cancer.gov/treatment/chemotherapy/sideeffects.html#:~:text=The%20fast%2Dgrowing%20norm al%20cells,%2C%20hair%20loss%2C%20and%20anemia. Consulted 22/08/23.
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