Secreted protein acidic and rich in cysteine (sparc) as chemotherapeutic sensitizers

Abstract

The present invention relates to compositions and methods of use thereof for cancer therapy sensitization. Such compositions comprise functional fragments of the nucleotide and/or polypeptide sequences of a Secreted Protein Acidic and Rich in Cysteine (SPARC). The compositions can be used in combination with existing chemotherapeutic agents for treatment of cancers.

1 .- 70 . (canceled) 
     
     
         71 . An isolated polypeptide selected from amino acids 17-153 of SEQ ID NO: 10, wherein the polypeptide has cancer therapeutic sensitizing activity. 
     
     
         72 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 3 and up to an additional 50 amino acids located the amino or carboxyl terminus or both termini of SEQ ID NO: 3. 
     
     
         73 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 3. 
     
     
         74 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 5 and up to an additional 50 amino acids located the amino or carboxyl terminus or both termini of SEQ ID NO: 5. 
     
     
         75 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 5. 
     
     
         76 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 7 and up to an additional 50 amino acids located the amino or carboxyl terminus or both termini of SEQ ID NO: 7. 
     
     
         77 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 7. 
     
     
         78 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 8 and up to an additional 50 amino acids located the amino or carboxyl terminus or both termini of SEQ ID NO: 8. 
     
     
         79 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 8. 
     
     
         80 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 9 and up to an additional 50 amino acids located the amino or carboxyl terminus or both termini of SEQ ID NO: 9. 
     
     
         81 . The isolated polypeptide of  claim 71 , wherein the polypeptide consists of SEQ ID NO: 9. 
     
     
         82 . A composition comprising one or more of the isolated polypeptides of any one of claims  1 - 11  and a pharmaceutically acceptable carrier. 
     
     
         83 . The composition of  claim 82 , further comprising a cancer therapeutic agent. 
     
     
         84 . The composition of  claim 83 , wherein the cancer therapeutic agent is selected from the group consisting of one or more chemotherapeutic agents, one or more radiotherapeutic agents, one or more alternative therapeutic agents, and combinations thereof. 
     
     
         85 . The composition of  claim 84 , wherein the chemotherapeutic agent is selected from the group consisting of one or more of mechlorethamine, cyclophosphamide, ifosfamide, melphalan (L-sarcolysin), chlorambucil; ethylenimines, methylmelamines, hexamethylmelamine and thiotepa; alkyl sulfonates, busulfan, nitrosoureas, carmustine (BCNU), semustine (methyl-CCNU), lomustine (CCNU) and streptozocin (streptozotocin), estramustine phosphate; triazines, dacarbazine (DTIC), dimethyl-triazenoimidazolecarboxamide, temozolomide, methotrexate (amethopterin), fluorouracin (5-fluorouracil), floxuridine (fluorodeoxyuridine, FUdR), cytarabine (cytosine arabinoside), gemcitabine; purine analogs, mercaptopurine (6-mercaptopurine, 6-MP), thioguanine (6-thioguanine), pentostatin (2′-deoxycoformycin, deoxycoformycin), cladribine and fludarabine, topoisomerase inhibitors, amsacrine, vinca alkaloids, vinblastine (VLB), vincristine; taxanes, paclitaxel, docetaxel (Taxotere), epipodophyllotoxins, etoposide, teniposide; camptothecins, topotecan, irinotecan, antibiotics, dactinomycin (actinomycin D), daunorubicin (daunomycin, rubidomycin), doxorubicin, bleomycin, mitomycin (mitomycin C), idarubicin, epirubicin, L-asparaginase, adrenocorticosteroids, prednisone, progestins, hydroxyprogesterone caproate, medroxyprogesterone acetate and megestrol acetate; estrogens such as diethylstilbestrol, ethinyl estradiol and related preparations; estrogen antagonists, tamoxifen, anastrozole; androgens, testosterone propionate, fluoxymesterone, androgen antagonists, flutamide, bicalutamid, gonadotropin-releasing hormone analogs, leuprolide, platinum coordination complexes, cisplatin, (cis-DDP), oxaliplatin, carboplatin; anthracenediones, mitoxantrone; substituted ureas, hydroxyurea, methylhydrazine derivatives, procarbazine (N-methylhydrazine, MIH); adrenocortical suppressants, mitotane (o,p′-DDD), aminoglutethimide; RXR agonists, bexarotene, tyrosine kinase inhibitors and imatinib and combinations thereof. 
     
     
         86 . The composition of claim  13 , wherein the chemotherapeutic agent is nanoparticulate, albumin bound paclitaxel.