Figure-1: Pathogenesis of cancer progression
The three stages of the carcinogenesis progression are initiation,
promotion, and progression. Additional exposure to genotoxic and
tumor-promoting substances speeds up the progression stage by increasing
genomic instability and cell proliferation rate, which transforms a
preneoplastic lesion into cancer. The genotoxic carcinogen produces
initiated cells with a mutant genotype during promotion, these cells are
stimulated to proliferate by tumour promoting carcinogens to form
clusters of initiated cells.
Animal models used in vitro and in vivo studies are crucial for
understanding the molecular mechanisms underlying tumour growth and
spread, identifying carcinogens, and screening chemotherapeutic drugs.
During the metastatic process, cancer cells can move or flow through a
number of micro environments, such as the stroma, blood vessel
endothelium, the vascular system, and tissue at a secondary location. As
a result, we have concentrated on the advanced models in this review
that have the potential to be used in cancer research.
In vivo models of cancer activity
Spontaneous tumour models, virus-induced tumour models,
radiation-induced tumour models, chemically induced tumour models,
transplantable tumour models, syngenic models, and xenogenic models are
among the in vivo models used to assess anticancer activity.
2.1 Spontaneous tumor models: It includes animals with a high
natural cancer rate, such as mice from specific inbred strains, which
are more prone to developing cancers such as breast cancer, leukaemia,
hepatomas and pulmonary adenomas(Ave and York, 1964). The endometrial
cancer kills more than 60% of female rats in the DA/Han strain.
Endometrial cancer kills 87 to 90 percent of BDII/Han rats(Vollmer,
2003). These models most closely match the clinical condition, as they
have kinetics and antigenicity that are similar to human malignancies.
For screening purposes, a sizable number of tumours of comparable size
cannot be obtained simultaneously. The tumours typically don’t manifest
until later in their progression, and the metastatic distribution is
rarely predictable, making accurate staging challenging. Most of these
models are discovered to be viral in nature, and they are rarely
replicable. Although such tumours offer a thorough evaluation of
anticancer effectiveness, they are rarely used for initial screening.
They are essential for molecular research on cancer and carcinogenesis.
(Vollmer, 2003).
2.2 Virus induced Tumor Models: The Friend leukaemia and Rous
sarcoma are the widely and most prevalent virus-induced cancers.
However, these models are rarely used in drug development(Vollmer, 2003)
2.2.1 Friend leukaemia: The Friend found this tumour in adult
Swiss mice for the first time. By injecting cell-free filtrates of
leukemic –spleen homogenates into other mice, it can be spread to other
mice. Various evaluation metrics include preventing splenic weight
increase, lowering the titer of live virus (as determined by bioassay),
and extending survival time. The 2 to 4 months’ time interval between
virus inoculation and the beginning of leukaemia makes evaluation
difficult and time-consuming, preventing these models from being
employed in antitumor screening studies.
2.2.2 Rous sarcoma: Rous was the first to report this tumour in
young chicks. It can be spread by implanting tumour pieces or
inoculating tumour homogenates with cell-free material. The most often
used evaluation measures are tumour growth inhibition and survival time.
The tumour growth can be more easily assessed because it is a localised
tumour. However, because it is insensitive to a wide range of agents, it
is possible that it will overlook the action of essential molecules.
2.3 Radiation-induced tumors: UV radiation is known to cause
cancer. This fact is utilised to generate tumor in laboratory animals by
exposing them to specific quantities of radiation, especially in case of
skin cancers. Radiation is sometimes employed in conjunction with other
chemical agents such as TPA or DMBA. The UV-induced skin carcinogenesis
in the SKH-1 hairless mouse and two-stage skin tumorigenesis models are
the two examples of radiation-induced tumour models. One advantage of
these models is that tumours develop on the skin, making them plainly
visible. The researcher may be exposed to radiation if radiation is
used, which is a serious limitation. Furthermore, the disadvantages of
this sort of model include the extended tumour induction period and the
time-consuming evaluation parameters. Based on the evaluation criteria
used, this type of model can be used to predict the overall
effectiveness of an anticancer drug. These models are not used in
routine screening programmes.