Gendicine

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Gendicine is a recombinant serotype 5 adenovirus used to overexpress functional p53 genes into individuals who have lost p53 function and have cancerous tissues growing. Gendicine works by targeting areas of cancerous growth and infiltrating the cells to supply the missing gene for p53 through homologous recombination. By supplying p53, Gendicine induces apoptosis throughout the cell[1]. Gendicine is genetically engineered to be missing certain proteins and as a result of these proteins missing, Gendicine's ability to replicate is inhibited. This is done to ensure that only the target tissue is getting an over expression of p53 but also means that Gendicine will need to be taken several times to be successful[2].

Only China's State Food and Drug Administration (SFDA) has approved the drug while, at the same time, Gendicine has been rejected by all other countries, most notably the United States of America and its FDA. The reasoning behind this comes from how the Gendicine clinical trials were conducted. In these clinical trials, only 135 patients were used, a much lower patient count then the minimum that would be needed to pass a novel drug in the United States[3]. For the FDA, there are several phases of clinical studies that must be completed before a drug can be approved. In the final phase, thousands of people with the disease or condition must be used. This is a far greater number than what is being used for Gendicine[4].

Gendicine has a very low number of side effects that occur as a result of its use. The most prevalent side effect is a high fever, which is thought to be caused by the increase in the immune system as a result of in increased cell death by p53 over expression[1].

When the gene for p53 activates, it will cause several pathways to also be activated, all of which are unique. Three of these pathways are the p21 gene pathway, BAX pathway and DRAM pathway. All three of these pathways result in different types of cell death. The p21 pathway will cause the cell to undergo cell cycle arrest, the BAX pathway causes apoptosis and the DRAM pathway results in the cell being engulfed through autophagy[5]. For the tumor cells that Gendicine is targeting, p53 will also inhibit the tumor's ability to carry out angiogenesis. p53 will most commonly block the angiogenesis process by inhibiting the expression of a vascular endothelial growth factor (VEGF) which is essential for angiogenesis to occur[1].

When p53 is activated in targeted cells, other non-targeted cells which are in close proximity may also take up the adenovirus and begin to over express p53. This is known as the bystander effect. This is not necessarily an event that will want to be avoided because when this occurs, it makes the tumor more susceptible to other kinds of treatments such as chemotherapy and radiotherapy. This claim has been supported by several trials where higher percentages of patient survival and tumor remission are present in the trials with mixed Gendicine and chemotherapy treatment compared to solely Gendicine or chemotherapy trials[1].

  1. ^ a b c d Li, Yi; Li, Bo; Li, Chun-Jie; Li, Long-Jiang (11 June 2015). "Key points of basic theories and clinical practice in rAd-p53 (Gendicine™) gene therapy for solid malignant tumors". Expert Opinion on Biological Therapy. 15 (3): 437–454. doi:10.1517/14712598.2015.990882.
  2. ^ Tazawa, Hiroshi; Kagawa, Shunsuke; Fujiwara, Toshiyoshi (23 May 2015). "Advances in adenovirus-mediated p53 cancer gene therapy". Expert Opinion on Biological Therapy. 13 (11): 1569–1583. doi:10.1517/14712598.2013.845662.
  3. ^ Jia, Hepeng. "Gene dreams troubled by market realities". rsc.org.
  4. ^ "Clinical Research". www.fda.gov.
  5. ^ Chen, Guang-Xia; Zhang, Shu; He, Xiao-hua; Liu, Shi-yu; Ma, Chao; Zou, Xiao-Ping (October 2014). "Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives". OncoTargets and Therapy: 1901. doi:10.2147/OTT.S50483.{{cite journal}}: CS1 maint: unflagged free DOI (link)