Our isogenic cell culture model suggests that KRAS mutations in SW48 colorectal cancer cells are linked to resistance to the multityrosine kinase inhibitor sunitinib. KRAS G13D mutant SW48 cells represented the KRAS subspecies with the lowest grade of resistance. Future studies will have to clarify whether KRAS can be used to guide sunitinib treatment or-in general-a treatment with a multityrosine kinase inhibitor in mCRC.
In this review we summarise the recent developments regarding the experimental and clinical use of mesenchymal stem cells (MSCs), focusing mainly on the treatment of gastrointestinal disorders. Next to their relevance in the field of regenerative medicine and immunology, this population of cells has also raised great expectations for possible applications in cancer therapy. While clinical trials were able to demonstrate the efficacy of MSCs in cases of inflammatory bowel disease and degenerative conditions of the liver, controversial results have been presented regarding their antineoplastic potential in gastrointestinal tumours. MSCs can differentiate into a large variety of specialised cells. They are capable of regulating both wound healing and immune responses through paracrine and endocrine signalling. Moreover, MSCs can be transfected with a great number of different therapeutic genes - considering their ability to selectively migrate towards neoplastic tissues, this feature allows for targeted therapy of solid tumours. Transfected genes can be designed so that they are expressed exclusively in the vicinity of the tumour, eventually triggering apoptosis in cancer cells. In this review, we demonstrate the natural distribution of exogenously applied MSCs in the host. Furthermore, we mention various methods of tracking MSCs in vivo and different parameters of administration that tend to influence therapeutic outcome (e.g., origin of MSCs, mode of application, or the potency of transfected genes). Finally, this review points out the hazards of MSC therapy, emphasising the risks related to their widespread clinical use.
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