**1. Introduction**

Neoplastic cells' capacity to spread and colonize distant tissues is their most dangerous trait. Most malignancies are curable when detected early and have not spread outside of the original tissue. However, cancer is frequently incurable when tumor cells have created colonies elsewhere. Tumor progression is the transformation of a healthy cell into a metastatic cancer cell that poses a threat to life. Neoplasia is a cellular illness, and research has been done to better understand the molecular mechanisms underlying the early stages of the progression that lead to the formation of cancer. The molecular mechanisms underpinning the behavioral changes that distinguish a metastatic cell from cells that are still at the site of tumor formation are now understood to reflect a fraction of cells that have left the primary tumor and are known as metastases [1, 2].

Tumor cells go through predominant steps and reach metastasis: invasion, intravasation, delivery, extravasation, and metastatic colonization. Further, tumor cells communicate with the surrounding microenvironment or tumor-associated stroma [3]. Tumor microenvironment affects tumor cells' metastatic ability and subpopulation of cancer stem cells, angiogenic vascular cells, cancer-associated fibroblasts, and infiltrating immune cells, the process additionally affects primary tumor metastatic capacity to distant locations [2, 4].

The spread of malignant cells to distant or disjointed secondary sites, where they multiply to create a mass, is known as metastasis. For almost every characteristic that is measured, tumor heterogeneity exists [1–3]. Positional, temporal, and genetic heterogeneity are the three forms that can exist inside a tumor. The accessibility of a cell to heterogeneous extrinsic stimuli influences positional heterogeneity. Regarding alterations in cells brought on by cycle signals, temporal heterogeneity is important. Genetic diversity is a result of the characteristics that tumor cells have by nature. Single-cell clone isolation proves that there are fundamental variations among the subpopulations that make up a single tumor mass [1].
