Compounds and methods for treating cancer

1. A compound for treating cancer comprising:

an anti-cancer chemotherapeutic agent linked to

an insulin-like growth factor-1 (IGF-1) receptor ligand;

wherein the IGF-1 receptor ligand is a variant IGF-1 that has reduced binding affinity for soluble IGF-1 binding proteins compared to wild-type IGF-1;

wherein the variant IGF-1 comprises the polypeptide structure A 1 -A 2 -A 3 -A 4 -LCG-A 5 -A 6 -LV-A 7 -AL-A 8 -A 9 -R 1 , wherein

A1 is FV;

A2 is N;

A3 is Q;

A4 is H;

A5 is S;

A6 is H;

A7 is E;

A8 is Y;

A9 is L; and

R1 is SEQ ID NO:6;

provided the variant IGF-1 does not consist of SEQ ID NO:1.

2. The compound of claim 1 wherein the chemotherapeutic agent is amsacrine, azacytidine, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytarabine, dactinomycin, daunorubicin, decarbazine, docetaxel, doxorubicin, epirubicin, estramustine, etoposide, floxuridine, fludarabine, fluorouracil, gemcitabine, hexamethylmelamine, idarubicin, ifosfamide, irinotecan, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin C, mitotane, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, pentostatin, plicamycin, procarbazine, ralitrexed, semustine, streptozocin, temozolamide, teniposide, thioguanine, thiotepa, topotecan, trimitrexate, valrubicin, vincristine, vinblastine, vindestine, or vinorelbine.

3. The compound of claim 1 wherein the chemotherapeutic agent is an anti-metabolite.

4. The compound of claim 1 wherein the anti-cancer chemotherapeutic agent is linked to the IGF-1 receptor ligand by a linkage comprising an amide bond.

5. The compound of claim 1 wherein the anti-cancer chemotherapeutic agent is linked to the variant IGF-1 through an amino group of the variant IGF-1.

6. The compound of claim 3 wherein the anti-metabolite is methotrexate.

7. The compound of claim 1 wherein the anti-cancer chemotherapeutic agent is doxorubicin.

8. A pharmaceutical composition comprising a compound of claim 1 .

9. A compound for treating cancer comprising:

an anti-cancer chemotherapeutic agent linked to an insulin-like growth factor-1 (IGF-1) receptor ligand;

wherein the IGF-1 receptor ligand is a variant IGF-1 that has reduced binding affinity for soluble IGF-1 binding proteins compared to wild-type IGF-1;

wherein the variant IGF-1 comprises SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10.

10. The compound of claim 9 wherein the variant IGF-1 is SEQ ID NO:4.

11. The compound of claim 9 wherein the chemotherapeutic agent is amsacrine, azacytidine, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytarabine, dactinomycin, daunorubicin, decarbazine, docetaxel, doxorubicin, epirubicin, estramustine, etoposide, floxuridine, fludarabine, fluorouracil, gemcitabine, hexamethylmelamine, idarubicin, ifosfamide, irinotecan, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin C, mitotane, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, pentostatin, plicamycin, procarbazine, ralitrexed, semustine, streptozocin, temozolamide, teniposide, thioguanine, thiotepa, topotecan, trimitrexate, valrubicin, vincristine, vinblastine, vindestine, or vinorelbine.

12. The compound of claim 9 wherein the chemotherapeutic agent is an anti-metabolite.

13. The compound of claim 9 wherein the anti-cancer chemotherapeutic agent is linked to the IGF-1 receptor ligand by a linkage comprising an amide bond.

14. The compound of claim 9 wherein the anti-cancer chemotherapeutic agent is linked to the variant IGF-1 through an amino group of the variant IGF-1.

15. The compound of claim 12 wherein the anti-metabolite is methotrexate.

16. The compound of claim 9 wherein the anti-cancer chemotherapeutic agent is doxorubicin.

17. pharmaceutical composition comprising a compound of claim 9 .