Methods for Detection and Elimination of Dormant Cancer Stem Cells (SD2012-080, 2012-081)
To inhibit the dormancy of therapeutically resistant LSC, methods: identify and functionally characterize LSC based on RNA isoform patterns, andtreat patients via a novel therapeutic strategy that sensitizes LSC to tyrosine kinase inhibitors and spares normal hematopoietic progenitors. Specifically, this approach may revive the ability to use classic BCR-ABL inhibitors to treat patients that are refractory to this standard of care.
Various agents that inhibit the Shh pathway may revive the ability to use classic tyrosine kinase inhibitors to treat patients that have become refractory to this standard of care. In addition, while validation is for CML, this may be useful for any cancer with an etiology based in changes in Shh signaling and may be used to sensitize patients to radiation therapy in addition to chemotherapeutic agents.
UC inventors found that by inhibiting the Shh pathway (validated for Smo inhibition), dormant cancer stem cells could be forced back into the cell cycle where they again become susceptible to BCR-ABL tyrosine kinase inhibitors (e.g., imatinib and dasatinib). And, because the stages of disease are characterized by predictable RNA isoform patterns, the levels of specific RNA isoforms and downstream gene products comprise companion indicators of CML progression and the likelihood of response to current therapeutic options.
Disease Diagnostic/Treatment
Cancer/Tumor
9611330
State Of Development In humanized, murine models of CML, inventors have identified RNA isoforms and levels of specific gene products that correlate with the stage of disease progression (chronic, blast crisis) and have found that these characteristic profiles reflect the physiologic changes that accompany treatment with a Smoothened (Smo) inhibitor. These findings are supported by studies that showed that dormant blast crisis CML stem cells re-entered the cell cycle when treated with a Smo inhibitor. Intellectual Property Info Worldwide rights available for licensure (See WO2013036867) Related Materials Tech ID/UC Case 23555/2012-037-2 Related Cases 2012-037-2, 2012-037-2, 2012-080-0, 2012-084-0
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