Sparc and methods of use thereof

Abstract

The invention provides methods for predicting or determining the response of a mammalian tumor to a chemotherapeutic agent and for treating a mammalian tumor comprising detecting and quantifying the SPARC protein or RNA in a sample isolated from the mammal. The invention further provides kit for predicting the response of a mammalian tumor to a chemotherapeutic agent, comprising a means for the isolation of protein or RNA from the tumor, a SPARC protein or RNA detection and quantification means, control RNAs, and rules for predicting the response of the tumor based on the level of SPARC protein or RNA in tumor.

What is claimed is: 
     
         1 . A method for predicting the response of a mammalian tumor to a chemotherapeutic agent or other anticancer agent comprising
 a. isolating a biological sample from the mammal,   b. detecting the expression of SPARC protein or RNA in the biological sample, and   c. quantifying the amount of SPARC protein or RNA in the biological sample.   
     
     
         2 . The method of  claim 1 , wherein the biological sample is isolated from the tumor. 
     
     
         3 . The method of  claim 1 , wherein the biological sample is isolated from a bodily fluid. 
     
     
         4 . The method of  claim 3 , wherein the bodily fluid is selected from the group consisting of cerebrospinal fluid, blood, plasma, serum, and urine. 
     
     
         5 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         6 . The method of  claim 1 , wherein SPARC protein or RNA is overexpressed in the tumor relative to the corresponding normal tissue. 
     
     
         7 . The method of  claim 1 , wherein the tumor is selected from the group consisting of oral cavity tumors, pharyngeal tumors, digestive system tumors, respiratory system tumors, bone tumors, cartilaginous tumors, bone metastases, sarcomas, skin tumors, melanoma, breast tumors, genital system tumors, urinary tract tumors, orbital tumors, brain and central nervous system tumors, gliomas, endocrine system tumors, thyroid tumors, esophageal tumors, gastric tumors, small intestinal tumors, colonic tumors, rectal tumors, anal tumors, liver tumors, gall bladder tumors, pancreatic tumors, laryngeal tumors, tumors of the lung, bronchial tumors, non-small cell lung carcinoma, small cell lung carcinoma, uterine cervical tumors, uterine corpus tumors, ovarian tumors, vulvar tumors, vaginal tumors, prostate tumors, prostatic carcinoma, testicular tumors, tumors of the penis, urinary bladder tumors, tumors of the kidney, tumors of the renal pelvis, tumors of the ureter, head and neck tumors, parathyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma, multiple myeloma, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia. 
     
     
         8 . The method of  claim 1 , wherein the chemotherapeutic or anticancer agent is selected from the group consisting of docetaxel, paclitaxel, taxanes, platinum compounds, antifolates, antimetabolites, antimitotics, DNA damaging agents, proapoptotics, differentiation inducing agents, antiangiogenic agents, antibiotics, hormones, peptides, antibodies, and combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the chemotherapeutic agent comprises particles of protein-bound drug. 
     
     
         10 . The method of  claim 9 , wherein the protein component of the protein-bound drug particles comprises albumin. 
     
     
         11 . The method of  claim 10 , wherein the chemotherapeutic agent comprises particles of albumin-bound paclitaxel. 
     
     
         12 . The method of  claim 11 , wherein more than 50% of the chemotherapeutic agent is in nanoparticle form. 
     
     
         13 . The method of  claim 12 , wherein the response of a mammalian tumor to a chemotherapeutic agent is positively correlated with SPARC levels. 
     
     
         14 . The method of  claim 13 , wherein the biological sample is isolated from the tumor. 
     
     
         15 . The method of  claim 11 , wherein the paclitaxel dose is from about 30 mg/m 2  to about 1000 mg/m 2  with a dosing cycle of about 3 weeks. 
     
     
         16 . The method of  claim 1 , wherein the response of a mammalian tumor to a chemotherapeutic agent is negatively correlated with SPARC levels. 
     
     
         17 . The method of  claim 16 , wherein the biological sample is isolated from the tumor. 
     
     
         18 . The method of  claim 1 , wherein the expression of SPARC protein is detected with an antibody. 
     
     
         19 . The method of  claim 1 , wherein the expression of SPARC protein is detected without an antibody. 
     
     
         20 . The method of  claim 1 , wherein the expression of SPARC protein is detected with a non-antibody SPARC binding molecule. 
     
     
         21 . The method of  claim 1 , wherein the expression of SPARC protein is detected without using a SPARC binding molecule. 
     
     
         22 . The method of  claim 1 , wherein in the SPARC RNA is detected by in situ hybridization, RNA amplification, Northern blot, microarray analysis or combinations thereof. 
     
     
         23 . A method of treating a tumor in a mammal with a chemotherapeutic agent or other anticancer agent comprising:
 a. isolating a biological sample from the mammal,   b. detecting the expression of SPARC protein or RNA in the biological sample,   c. quantifying the amount of SPARC protein or RNA in the biological sample,   d. determining if the SPARC protein or RNA is present at a level indicating the administration of the chemotherapeutic agent or other anticancer agent to the mammal, and   e. administering to the mammal a therapeutically effective amount of the chemotherapeutic agent or other anticancer agent.   
     
     
         24 . The method of  claim 23 , wherein the chemotherapeutic agent is select from the group consisting of docetaxel, paclitaxel, taxanes, platinum compounds, antifolates, antimetabolites, antimitotics, DNA damaging agents, proapoptotics, differentiation inducing agents, antiangiogenic agents, antibiotics, hormones, peptides, antibodies, and combinations thereof. 
     
     
         25 . The method of  claim 23 , wherein the chemotherapeutic agent comprises particles of protein-bound drug. 
     
     
         26 . The method of  claim 25 , wherein the protein component of the protein-bound drug particles comprises albumin. 
     
     
         27 . The method of  claim 26 , wherein the chemotherapeutic agent comprises particles of albumin-bound paclitaxel. 
     
     
         28 . The method of  claim 27 , wherein more than 50% of the chemotherapeutic agent is in nanoparticle form. 
     
     
         29 . The method of  claim 28 , wherein the paclitaxel dose is from about 30 mg/m 2  to about 1000 mg/m 2  with a dosing cycle of about 3 weeks. 
     
     
         30 . The method of  claim 23 , wherein the mammal is a human. 
     
     
         31 . The method of  claim 23 , wherein the tumor is a carcinoma of the breast, ovary, head and neck, colon, prostate, bladder or kidney. 
     
     
         32 . A kit for predicting the response of a mammalian tumor to a chemotherapeutic agent or other anticancer agent, comprising
 a. a means for the isolation of protein from the tumor,   b. a SPARC protein detection and quantification means,   c. control proteins, and   d. rules for predicting the response of the tumor.   
     
     
         33 . The kit of  claim 32 , wherein the chemotherapeutic agent comprises particles of albumin-bound drug and more than 50% of the chemotherapeutic agent is in nanoparticle form. 
     
     
         34 . The kit of  claim 33 , wherein the albumin-bound drug is paclitaxel. 
     
     
         35 . A kit for predicting the response of a mammalian tumor to a chemotherapeutic agent or other anticancer agent, comprising
 a. a means for the isolation of RNA from the tumor,   b. a SPARC RNA detection and quantification means,   c. control RNAs, and   d. rules for predicting the response of the tumor based on the level of SPARC RNA in tumor.   
     
     
         36 . The kit of  claim 35 , wherein the chemotherapeutic agent comprises particles of albumin-bound drug and more than 50% of the chemotherapeutic agent is in nanoparticle form. 
     
     
         37 . The kit of  claim 36 , wherein the albumin-bound drug is paclitaxel. 
     
     
         38 . A method for delivering a therapeutic agent to a disease site in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the therapeutic agent coupled to a compound capable of binding an albumin-binding protein and a pharmaceutically acceptable carrier, provided that the pharmaceutical composition does not comprise more than 50% of the therapeutic agent in nanoparticle form. 
     
     
         39 . The method of  claim 38 , wherein the pha inaceutical composition does not comprise more than 10% of the therapeutic agent in nanoparticle form. 
     
     
         40 . The method of  claim 38 , wherein the pharmaceutical composition does not comprise more than 5% of the therapeutic agent in nanoparticle form. 
     
     
         41 . The method of  claim 38 , wherein the albumin-binding protein is a SPARC protein. 
     
     
         42 . The method of  claim 38 , wherein the disease site is a tumor. 
     
     
         43 . The method of  claim 38 , wherein the therapeutic agent is a diagnostic agent. 
     
     
         44 . The method of  claim 43 , wherein the diagnostic agent is selected from the group consisting of radioactive agents, MRI contrast agents, X-ray contrast agents, ultrasound contrast agents, and PET contrast agents. 
     
     
         45 . The method of  claim 38 , wherein the compound is a ligand that binds the SPARC protein. 
     
     
         46 . The method of  claim 45 , wherein the ligand is selected from the group consisting of a calcium cation (Ca2+), copper cation (Cu2+), iron cation (Fe2+), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), collagen I, collagen II, collagen III, collagen IV, collagen V, collagen IX, vitronectin, thrombospondin-1, endothelial cells, platelets, albumin, and hydroxyapatite. 
     
     
         47 . The method of  claim 38 , wherein the compound capable of binding an albumin-binding protein is a small molecule. 
     
     
         48 . The method of  claim 47 , wherein the small molecule is selected from the group consisting of a chemical, a protein, and a carbohydrate. 
     
     
         49 . The method of  claim 38 , wherein the compound capable of binding an albumin-binding protein is an antibody to the SPARC protein. 
     
     
         50 . The method of  claim 42 , wherein the tumor is located in the bladder, liver, ovary, kidney, gut, brain, or breast. 
     
     
         51 . The method of  claim 38 , wherein the mammal is a human. 
     
     
         52 . The method of  claim 38 , wherein the route of administration is selected from the group consisting of intravenous, intraperitoneal, intratumoral, and inhalational. 
     
     
         53 . The method of  claim 49 , wherein the antibody is a polyclonal antibody. 
     
     
         54 . The method of  claim 49  wherein the antibody is manufactured in an animal selected from the group consisting of a chicken, rat, mouse, rabbit, guinea pig, hamster, sheep, cow, and goat. 
     
     
         55 . The method of  claim 49 , wherein the antibody is monoclonal. 
     
     
         56 . The method of  claim 55 , wherein the antibody is humanized. 
     
     
         57 . The method of  claim 55 , wherein the antibody is manufactured by fusion of a single cell line producing anti-SPARC antibody with a myeloma line. 
     
     
         58 . The method of  claim 55 , wherein the antibody is made in vitro by a method selected from the group consisting of a peptide synthesizer, by conversion of display phage into antibody, and mutagenesis or synthesis of variable regions of the heavy and light chain genes for antibody. 
     
     
         59 . The method of  claim 55 , wherein the antibody is selected from the group consisting of monovalent, multivalent; monospecific, bispecific, single chain, and a Fab fragment. 
     
     
         60 . The method of  claim 55 , wherein the antibody is a chimera. 
     
     
         61 . The method of  claim 49 , wherein the therapeutic agent is an antibody which mediates complement activation and cell mediated cytotoxicity against the tumor. 
     
     
         62 . The method of  claim 38 , wherein the therapeutic agent is selected from the group consisting of tyrosine kinase inhibitors, kinase inhibitors, biologically active agents, biological molecules, radionuclides, adriamycin, ansamycin antibiotics, asparaginase, bleomycin, busulphan, cisplatin, carboplatin, carmustine, capecitabine, chlorambucil, cytarabine, cyclophosphamide, camptothecin, dacarbazine, dactinomycin, daunorubicin, dexrazoxane, docetaxel, doxorubicin, etoposide, epothilones, floxuridine, fludarabine, fluorouracil, gemcitabine, hydroxyurea, idarubicin, Ifosfamide, irinotecan, lomustine, mechlorethamine, mercaptopurine, meplhalan, methotrexate, rapamycin (sirolimus), mitomycin, mitotane, mitoxantrone, nitrosurea, paclitaxel, pamidronate, pentostatin, plicamycin, procarbazine, rituximab, streptozocin, teniposide, thioguanine, thiotepa, taxanes, vinblastine, vincristine, vinorelbine, taxol, combretastatins, discodermolides, transplatinum, anti-vascular endothelial growth factor compounds (“anti-VEGFs”), anti-epidermal growth factor receptor compounds (“anti-EGFRs”), 5-fluorouracil and derivatives and combinations thereof. 
     
     
         63 . The method of  claim 62 , wherein the therapeutic agent is a kinase inhibitor. 
     
     
         64 . The method of  claim 63 , wherein the kinase inhibitor is genistein. 
     
     
         65 . The method of  claim 38 , wherein the therapeutic agent is a biological molecule. 
     
     
         66 . The method of  claim 65 , wherein the biological molecule is selected from the group consisting of tTF and TNF. 
     
     
         67 . The method of  claim 38 , wherein the therapeutic agent is a radionuclide. 
     
     
         68 . The method of  claim 49 , wherein the tumor is located in the bladder, liver, ovary, kidney, gut, brain, or breast. 
     
     
         69 . The method of  claim 49 , wherein the mammal is a human. 
     
     
         70 . The method of  claim 49 , wherein the route of administration is intravenous, intraperitoneal, intratumoral, or inhalational. 
     
     
         71 . A method for delivering a chemotherapeutic agent to a tumor in a mammal, wherein the method comprises administering to a mammal a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a chemotherapeutic agent coupled to a SPARC protein capable of binding albumin and a phai inaceutically acceptable carrier. 
     
     
         72 . The method of  claim 71 , wherein the SPARC is purified using chromatography. 
     
     
         73 . The method of  claim 72 , wherein the chromatography is selected from the group consisting of ionic, size exclusion, or C-18 chromatography. 
     
     
         74 . The method of  claim 23 , wherein the other anticancer agent is an anti-SPARC antibody.