Methods for treating chemoresistant cancer-initiating cells
The disclosure provides methods of treating cancer by selectively inhibiting p-S 552 -β-catenin, p-T 217 -β-catenin, p-T 332 -β-catenin, and/or p-S 675 -β-catenin production and/or activity. Such methods also and/or limit cancer-initiating cells.
1. A method of treating leukemia, comprising administering to a subject that has leukemia resistant to radiation therapy, chemotherapy, immunotherapy, or any combination thereof a pharmaceutically active molecule that is capable of selectively inhibiting one or more of p-S 552 -β-catenin, p-T 217 -β-catenin, p-T 332 -β-catenin, or p-S 675 -β-catenin production or activity, wherein the pharmaceutically active molecule is administered in an amount effective to reduce or limit leukemia-initiating cells, wherein the pharmaceutically active molecule is administered in one or more nanoparticle compositions comprising a block copolymer in a core/shell form, wherein the block copolymer comprises:
wherein
x is an integer between about 3 and about 100;
m is an integer between about 5 and about 200; and
n is an integer between about 5 and about 100.
2. The method of claim 1 , wherein the pharmaceutically active molecule is administered in a low dose.
3. The method of claim 2 , wherein the subject is a human subject, and the low dose is about ⅕ to 1/50 of a human clinical dose of the pharmaceutically active molecule when dosed for chemotherapy.
4. The method of claim 1 , wherein the pharmaceutically active molecule is administered in a nanoparticle formulation.
5. The method of claim 1 , wherein the pharmaceutically active molecule is anthracycline, doxorubicin, daunorubicin, or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the pharmaceutically active molecule is doxorubicin, or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the doxorubicin is administered in a dose of up to about 10 mg/m 2 per day.
8. The method of claim 1 , comprising administering a combination of two different nanoparticle compositions.
9. The method of claim 8 , wherein a first nanoparticle composition comprises pharmaceutically active molecule that is-doxorubicin.
10. The method of claim 9 , wherein a second nanoparticle composition comprises pharmaceutically active molecule selected from the group consisting of daunorubicin, vincristine, epirubicin, idarubicin, valrubicin, mitoxantrone, paclitaxel, docetaxel, cisplatin, camptothecin, irinotecan, 5-fluorouracil, methotrexate, and dexamethasone.
11. The method of claim 1 , wherein the nanoparticle composition further comprises one or more metal nanoparticles or quantum dots.
12. A method of treating leukemia, comprising administering to a human subject in need thereof a pharmaceutically active molecule that is capable of selectively inhibiting one or more of p-S 552 -β-catenin, p-T 217 -β-catenin, p-T 332 -β-catenin, or p-S 675 -β-catenin production or activity, wherein the pharmaceutically active molecule is administered in an amount of about ⅕ to 1/50 of a human clinical dose of the pharmaceutically active molecule when dosed for chemotherapy, the amount effective to reduce or limit leukemia-initiating cells, wherein the pharmaceutically active molecule is administered in one or more nanoparticle compositions comprising a block copolymer in a core/shell form, wherein the block copolymer comprises:
wherein
x is an integer between about 3 and about 100;
m is an integer between about 5 and about 200; and
n is an integer between about 5 and about 100.