The most studied and best characterized of the known cancer-related genes is the RAS gene family. Kras, one of three human ras genes, is the most elusive to target pharmacologically due to 1) its prevalence in human cancers, 2) higher inherent chemotherapy resistance, 3) its well-stablished role in different cellular functions, 4) complicated interaction with other signaling pathways and 5) a lack of effective targeted therapy. Cancer stem cells found within tumors have the ability to self-renew and differentiate to all downstream cells. Studies showed that Krasmut (Kras mutation) activates the stem cell-like program during human cancers to transform human cancers. Krasmut has been suggested to induce malignant transformation by increasing cancer-initiating cells plasticity to bypass senescence. Krasmut imposes the embryonic stem cell-like program through the alternation of expression pattern of several genes involved in reprogramming of the cells. Considering Krasmut as a stem cell-like program driver, further characteristics of cancer stem cells related to specific signaling pathways induced by Krasmut and surface mark ers need to be elucidated. Some of the downstream signaling pathways have been found to be hyper activated in pancreatic cancer stem cells through active GTP-bound Kras which promotes cell survival, proliferation and cancer progression. In a study NVP-BEZ-235as a dual inhibitor of PI3K and mTOR complex I and complex II has shown anti-proliferative effects. Other results showed that miR145 an embryonic SC program inhibitor, significantly suppresses the tumorigenicity of KRASmut colon cancer cells by promoting cell lineage differentiation. In addition, some of the stem cell surface markers like CD133 and CD44 are potential targets to improve the efficiency of treating KRASmut cancer stem cells. These findings warrant that continued prospective studies are needed to provide adequate and unique diagnostic and therapeutic strategies for cancer patients with Kras mut.

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