2.6.2 Knockout Mice
A knockout animal is one in which both alleles of a certain gene are missing.
2.6.2.1 Nkx 3.1 knockout mice: A tumour suppressor gene called Nkx 3.1 is only present in the prostate. It is necessary for the prostate’s differentiation and operation. This gene’s inactivation results in histopathological anomalies that resemble human prostate cancer. The causes of prostate cancer as well as the disease’s tissue-specific characteristics can be studied using this mode(Brigelius-Flohé and Flohé, 2020).
2.6.2.2 Homozygous p53 knockout mice: A mutation in the p53 tumour suppressor gene is the most frequent genetic abnormality in human cancer. More than half of all human malignancies have p53 gene point mutations or deletions that can be identified. These mice have a tendency to develop spontaneous cancer, particularly lymphomas(Abate-Shen and Shen, 2002).
5.6.2.1 Brca1 conditional knockout model: By expressing Cre under the control of MMTV-LTR or WAP, the CreIoxp technique is used to induce Brca1 deletion. Animals between the ages of 10 and 13 develop mammary tumours.(Fargiano et al., 2003).
Even though patient-derived xenograft (PDX) models can quickly transfer original tumours while maintaining their integrity, in vitro and in vivo approaches frequently involve deconstructing and, in some cases, reconstructing the original tumours for the purpose of evaluating the subsequent medication response. Fresh tumour tissues collected without deconstruction or reconstruction are used to evaluate the efficacy of the therapy using ex vivo methods, such as patient-derived explant (PDE) models. The cell types that can be derived from and used are schematically shown in each model system. The use of mouse models greatly facilitates the discovery of novel cancer therapies. To characterise in vivo drug pharmacokinetics and pharmacodynamics (PK/PD), identify and validate novel cancer pathways and therapeutic targets, and assess in vivo anti-cancer efficacy of suggested treatments, preclinical research using mouse cancer models is required. Phase I-III clinical studies are carried out to assess the safety and anti-cancer efficacy of these drugs in human patients after positive preclinical outcomes. Due to innate or resistant mechanisms, a small subset of patients will have a poor response, these patients can be studied mechanistically in preclinical mouse models to find response biomarkers and combination therapies to treat or prevent resistance. The close coordination of mouse studies with human clinical trials will lead to improved patient classification, the discovery of novel biomarkers, and the development of suitable combination medicines, improving the care of cancer patients (Figure -2).