Systematic anti-cancer therapies
amount of monoclonal antibodies. 13 These monoclonal antibodies are even being used in conjunction with chemotherapy drugs in the treatment of HER2-positive breast cancer. Drugs such as ado- trastuzumab emtansine combine together the monoclonal antibody trastuzumab and the chemo drug emtansine which is used to treat early-stage breast cancer after surgery. This means that the chemotherapy drugs can be delivered directly to the cancerous cells attached to the constant region of the antibody reducing the effect on other normal fast-growing cells elsewhere in the body. 14
Prostate cancer
Prostate cancer is a hormonal cancer that initially responds well to hormonal treatments to block the testosterone pathway. After several years the tumours become castrate/hormone resistant and further options are required. One of these was originally developed for dealing with the BRCA gene mutations within breast and ovarian cancer. This mutation also occurs in prostate cancer cells such that the same treatment with the drug Olaparib or Rucaparib is effective. 15 These drugs are known as PARP inhibitors, which is an important protein in the repairing of DNA in particular base excision repairs (BERs) which removes bases that have been damaged by oxidation and replaces them. 16 When the PARP protein is inhibited the BERs are impaired, it leads to single stand breaks (SSBs) in the DNA which accumulate and eventually become double strand breaks (DSBs) which means these cells become increasingly dependent on other repair pathways. The BRCA codes for homologous recombination, another repair pathway, so when cancer cells already have a mutated BRCA gene meaning this repair pathway doesn ’t function correctly, the number of double stranded breaks continues to accumulate until the extent of the DNA damage kills the cell. Therefore, these PARP inhibitors can have increased potency when combined with chemotherapy drugs such as cisplatin, doxorubicin and etoposide as they induce SSBs and DSBs. 17 However, further research is required into prostate cancer targeted therapy as this is the only form of targeted therapy to treat prostate cancer.
13 Whitfield, K. In Vitro and In Vivo monoclonal antibody production. https://pivotalscientific.com/scientific-library/in-vitro-and-in-vivo-mab-production/. Consulted:24/08/23.
14 See note 11. 15 See Targeted drug therapy for prostate cancer
https://www.cancer.org/cancer/types/prostate-cancer/treating/targeted-therapy.html. Consulted 23/08/23; Prostate Cancer UK. Landmark moment: first gene-targeting treatment for prostate cancer on NHS, opens door to more targeted therapies in future at https://prostatecanceruk.org/about-us/news-and-views/2023/04/landmark-moment-first-gene-targeting-treatment- for-prostate-cancer-on-nhs-opens-door-to-more-targeted-therapies-in- future#:~:text=Olaparib%2C%20a%20drug%20that%20targets,several%20months%20longer%20on%20average. Consulted 23/08/23. 16 See Chen, A. (2011) ‘PARP inhibitors: its role in treatment of cancer’, Chin J Cancer 30(7): 463-471 & Krokan, H. (2013) ‘Base excision repair’, Cold Spring Harb Perspect Biol 5(4): a012583. 17 Singh, V. (2022) ‘Quantification of single -strand DNA lesions caused by the topoisomerase II poison etoposide using single DNA molecule imaging’, Biochemical and biophysical research communications 594: 57-62.
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