Targeting hypoxic cancer stem cells (CSCs) with doxycycline: implications for improving anti-angiogenic therapy
AssigneeLunella Biotech, Inc.
InventorsMichael P. Lisanti, Federica Sotgia
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Abstract
The present disclosure relates to inhibitors of mitochondrial function. Methods of treating hypoxic cancer cells using anti-angiogenic agents and mitochondrial biogenesis inhibitors are disclosed. Tetracyclines, such as doxycycline, may serve as mitochondrial biogenesis inhibitors. Also described are methods of sensitizing hypoxic cancer cells to one or more chemotherapies by administering a mitochondrial biogenesis inhibitor with the chemotherapy.
Claims16
A method of treating hypoxic cancer stem cells (CSCs) comprising:
- administering, to a cancer patient having chronic hypoxia, a therapeutically effective amount of an anti-angiogenic agent and a therapeutically effective amount of a mitochondrial biogenesis inhibitor,
- wherein the anti-angiogenic agent is selected from the group consisting of bevacizumab, itraconazole, carboxyamidotriazole, TNP-470, CM101, INF-alpha, IL-12, platelet factor-4, suramin, SU5416, thrombospondin, a VEGFR antagonist, an angiostatic steroid plus heparin, Cartilage-Derived Angiogenesis Inhibitory Factor, a matrix metalloproteinase inhibitor, angiostatin, endostatin, 2-methoxyestradiol, tecogalan, tetrathiomolybdate, thalidomide, thrombospondin, prolactin, linomide, αVβ3 inhibitors, ramucirumab, tasquinimod, ranibizumab, sorafenib, sunitinib, pazopanib, and everolimus;
- and
- the mitochondrial biogenesis inhibitor is selected from the group consisting of tetracycline, doxycycline, tigecycline, minocycline, eyrthromycin, azithromycin, clarithromycin, pyrvinium pamoate, atovaquone, bedaquiline, sorafenib, niclosamide, berberine, stiripentol, chloroquine, etomoxir, perhexiline, mitoriboscin, mitoketoscin, mitoflavoscin, TPP-compound, mDIVI1, caffeic acid phenyl ester, antimitoscin, and repurposcin.
A method of sensitizing hypoxic cancer stem cells CSCs to a chemotherapeutic agent, the method comprising:
- administering, to a cancer patient having chronic hypoxia, a therapeutically effective amount of a mitochondrial biogenesis inhibitor with a chemotherapeutic agent;
- and
- wherein the mitochondrial biogenesis inhibitor comprises at least one of a tetracycline, doxycycline, tigecycline, minocycline, eyrthromycin, azithromycin, clarithromycin, pyrvinium pamoate, atovaquone, bedaquiline, sorafenib, niclosamide, berberine, stiripentol, chloroquine, etomoxir, perhexiline, mitoriboscin, mitoketoscin, mitoflavoscin, TPP-compound, mDIVI1, caffeic acid phenyl ester, antimitoscin, and repurposcin.
A method of sensitizing hypoxic cancer stem cells (CSCs) to radiotherapy, the method comprising:
- administering, to a cancer patient having chronic hypoxia, a therapeutically effective amount of a mitochondrial biogenesis inhibitor with radiotherapy.
Dependencies are inferred from the claim text.