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.