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).