7. Metastasis
The most common cause of cancer death is metastasis, or the spread of
the primary lesion cell into the distal organs. A variety of cell
mechanisms are involved in the diffusion of cells from a primary tumour.
These include stromal invasion or collusion, immune avoidance by
inhibiting or co-opting anti-tumorigenic processes, tissue
microenvironment avoidance and modification, and the development
[88,89].
Figure -3 : An Overview of the Metastasis routes that
have been observed
A multiscale, intricate process called metastasis involves a number of
parallel sub processes travelling partially overlapping paths.
Premalignant lesions are not only associated with late-stage primary
tumours, according to recent studies, but they can also cause distant,
latent metastasis. It is still widely believed that metastasis mainly
results from cellular reprogramming events that speed up cell migration
and invasion toward more nutrient-rich niches when micro environmental
stressors drive cellular reprogramming processes. When different
stressors are combined with metabolic reprogramming, cancer cells can
experience phenotypic changes that allow them to adopt more malleable,
mesenchymal-like states rather than binary states. This allows the cells
to sample these dynamic states throughout the metastatic process. This
might make a cell more capable of proliferating, but it’s no longer
considered to be the main mechanism. Many different strategies are used
by cancer cells to achieve their goals. Although cancer does not have a
preference for any particular organs, lymphatics and blood vessels are
the most common entry points for cancer cells into metastatic organs
(lymph nodes, liver, lung, bone marrow, and brain). Cancer cell survival
and growth are influenced by a number of genetic and epigenetic changes,
as well as interactions with the intricate cell environment in the host
microenvironment [88,89].
8. Conclusion and Future perspectives: Spontaneous tumor models
have provided considerable insight into analysing natural illness
progression, despite not being especially beneficial in medication
research. Virus-induced tumours are no longer often used. Tumors caused
by chemicals or radiation have their own position in drug testing and
evaluation. However, due to some of their drawbacks (particularly the
protracted induction period), they are not suitable for use in
large-scale screening programmes. Transplantable tumours are the
greatest alternative in this situation, which demands short-term,
repeatable, and less expensive procedures due to which they have been
widely used in drug testing. Evaluation of the activity of the test drug
on a specific form of cancer is another significant component of cancer
research. Due to the use of cell lines, this type of screening has a lot
of flexibility (in vitro or in transplantable malignancies). The use of
genetically altered mouse models for disease-focused screening may be
feasible. However, they are primarily used to study the mechanisms of
carcinogenesis. A number of targeted therapeutic substances that have
shown promising results in clinical trials have been produced by the
application of these models. Each model consequently has a special set
of benefits and drawbacks. It is necessary to make full and appropriate
use of these assays in the drug discovery and therapy response
evaluation fields.
Acknowledgements: The author sincerely express thankful to NGSM
institute of pharmaceutical science and Nitte (Deemed to be university)
for the support.
Author contributions: Ashwini Prabhu, Revana Siddappa BC and BR
Prashantha Kumar, designed the review article;Undiganalu G. Yathishahas
designed the figure in article,Shridhar Narayan Deshpande and Mahendra
Gowdru Srinivasa prepared the manuscript.
Data availability: The datasets used or analysed during the
current study are available from the corresponding author upon
reasonable request.