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Simple Summary: The rising incidence of cancer is a major threat to patients and healthcare services worldwide. It is therefore important to search for novel therapies and new drugs. Honokiol, found in the bark of the magnolia tree, has many properties, including anticancer activity. However, its potential use is limited due to its poor solubility in water. The present study aimed to review the available studies using modern delivery systems for honokiol and determine their anticancer efficacy in vitro and in vivo. Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular mechanisms underlying the observed anticancer effects, emphasizing both in vitro and in vivo studies. The effects of HON application, primarily in the common types of cancers, are presented. Because the therapeutic potential of HON may be limited by its physicochemical properties, appropriate delivery systems are sought to overcome this problem. This review discusses the effect of different nanotechnology-based delivery systems on the efficiency of HON. The data presented show that HON exhibits anticancer effects and can be successfully administered to the site of action. Honokiol exerts its anticancer activity through several mechanisms. Moreover, some authors used the combinations of classical anticancer drugs with HON. Such an approach is very interesting and worth further investigation. Understanding HON's multiple molecular mechanisms would provide valuable insights into how HON might be developed as an effective therapeutic. Therefore, further research is needed to explore its specific applications and optimize its efficacy in diverse cancer types. [ABSTRACT FROM AUTHOR]

Simple Summary: Colon cancer is a solid tumor that is a prominent contributor to global mortality. Immune cells genetically engineered with a chimeric antigen receptor (CAR) that can recognize cancer-specific targets is a new innovative therapy approach that has had success in treating blood cancers but is still in development for treating solid tumors such as colon cancer. Part of the reason for the added difficulty in targeting solid tumors is the tumor microenvironment that acts as a protective barrier around a solid tumor. In this research paper, we have developed a new cellular approach for the targeted treatment of colon cancer that is designed to overcome the tumor microenvironment. We tested this new CAR cell therapy against multiple solid colon cancer models, and confirmed its efficacy and functionality in finding and eliminating solid tumors. Colorectal carcinoma (CRC) presents a formidable medical challenge, demanding innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising alternative to CAR T-cell therapy for cancer. A suitable tumor antigen target on CRC is carcinoembryonic antigen (CEA), given its widespread expression and role in tumorigenesis and metastasis. CEA is known to be prolifically shed from tumor cells in a soluble form, thus hindering CAR recognition of tumors and migration through the TME. We have developed a next-generation CAR construct exclusively targeting cell-associated CEA, incorporating a PD1-checkpoint inhibitor and a CCR4 chemokine receptor to enhance homing and infiltration of the CAR-NK-92 cell line through the TME, and which does not induce fratricidal killing of CAR-NK-92-cells. To evaluate this therapeutic approach, we harnessed intricate 3D multicellular tumor spheroid models (MCTS), which emulate key elements of the TME. Our results demonstrate the effective cytotoxicity of CEA-CAR-NK-92 cells against CRC in colorectal cell lines and MCTS models. Importantly, minimal off-target activity against non-cancerous cell lines underscores the precision of this therapy. Furthermore, the integration of the CCR4 migration receptor augments homing by recognizing target ligands, CCL17 and CCL22. Notably, our CAR design results in no significant trogocytosis-induced fratricide. In summary, the proposed CEA-targeting CAR-NK cell therapy could offer a promising solution for CRC treatment, combining precision and efficacy in a tailored approach. [ABSTRACT FROM AUTHOR]