As per the information derived from GLOBOCAN 2018, CRC is a deadly and frequently diagnosed cancer of the colon and rectum, excluding the anus [1]. The projected number of cases of CRC across the United States for 2021 was 1,49,500, whereas the projected number of deaths was 52,980 [2]. Consequently, 1,51,030 new cases and 52,580 deaths are expected for 2022 [3]. Interestingly, a low CRC burden is observed in China in comparison to the global level [4], [5]. The Chinese Cancer Registration Report for 2018 created based on the National Cancer Center data concluded that 3,87,600 new cases and 1,87,100 deaths in 2015 were linked to CRC across China, in which the occurrence rate was higher in men over 50 years of age [6]. Recently, a pattern of a higher prevalence of CRC was observed in young adults than in elderly people [7].

The extracellular matrix (ECM) is a cell-free, three-dimensional component of every tissue and organ, necessary for the physical scaffolding of cellular elements. This scaffolding is vital for cell-to-cell interactions and is responsible for cellular growth, survival, tissue formation and homeostasis [8]. Primarily, the ECM comprises water, fibrous proteins, proteoglycans (filling the interstitial space) and polysaccharides (maintaining the structural integrity of the ECM) [9]. The changes at the molecular level via epithelial-mesenchymal transition (EMT) result in the breakdown of ECM and the dissemination of malignant cells, consequently leading to an elevated metastatic potential [10].

Anoikis is a type of programmed cell death closely related to apoptosis with similar pathways and components. However, it is generated under conditions where the cell interacts inappropriately with its ECM matrix or after detaching from it [11]. If the cancer cells acclimatize to an environment different from their original environment, they are termed anchorage-independent and are most likely anoikis-resistant. By virtue of their abilities to resist anoikis and grow independent of anchorage, they can spread into nearby tissues and metastasize throughout the body [12]. After being discovered in 1994 by Frisch and Francis, anoikis has been studied extensively, and cells, especially those that are cancerous, have been found to be resistant to anoikis in circulation by adapting several mechanisms. Thus, stimulating anoikis has turned out to be a key technique for inhibiting cancer cell metastasis [13]. Anoikis resistance (AR) induces several biochemical and molecular changes at the cellular level that remain hallmarks of invasive and metastatic properties and support resistance to therapy and relapse among malignant cells [14].

A therapeutic agent is usually expected to promote anoikis or sensitize resistant cancer cells to anoikis in cancer therapy [15]. For this purpose, the identification of therapeutic targets and biomarkers remains critical [16]. Although several biomarkers are preferably used as diagnostic and prognostic tools, some are used as therapeutic targets [17]. Hence, the present review focuses on analyzing the roles of anoikis in CRC therapy and identifying anoikis-regulating molecules as therapeutic targets for CRC.