Nanoparticles and distinct exosome subsets for detection and treatment of cancer

Abstract

The present invention is directed to methods of diagnosing, prognosing, and managing treatment of cancer in a subject. These methods involve selecting a subject having cancer and obtaining, from the selected subject a population of either exomeres having a diameter less than 50 nm, small exosomes having a diameter of 60-80 nm, or large exosomes having a diameter of 90-120 nm, The exomeres, small exosomes, or large exosomes are recovered from the sample, and the exomeres, small exosomes, or large exosomes or portions thereof are contacted with one or more reagents suitable to detect: (1) higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more proteins contained in said exomeres, small exosomes, or large exosomes, (2) higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more N-giyeans contained In said exomeres, small exosomes, or large exosomes, (3) higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or mom lipids contained in said exomeres, small exosomes, or large exosomes, (4) the presence or absence of one or mom genetic mutations in nucleic acid molecules associated with cancer and contained in said exomeres, small exosomes, or large exosomes, or (5) combinations thereof. Cancer is then diagnosed, prognosed, or treatment Is modified based on this information.

1 . A method of diagnosing cancer in a subject, said method comprising:
 selecting a subject having cancer;   obtaining, from the selected subject, a population of either exomeres having a diameter of less than 50 nm, small exosomes having a diameter of 60-80 nm, or large exosomes having a diameter of 90-120 nm;   recovering the exomeres, small exosomes, or large exosomes from the sample;   contacting the exomeres, small exosomes, or large exosomes or portions thereof with one or more reagents suitable to detect: (1) higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more proteins contained in said exomeres, small exosomes, or large exosomes, (2) higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more N-glycans contained in said exomeres, small exosomes, or large exosomes, (3) higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more lipids contained in said exomeres, small exosomes, or large exosomes, (4) the presence or absence of one or more genetic mutations in nucleic acid molecules associated with cancer and contained in said exomeres, small exosomes, or large exosomes, or (5) combinations thereof, and   diagnosing the cancer based on said contacting.   
     
     
         2 . The method of  claim 1 , wherein said sample is blood, serum, plasma, ascites, cyst fluid, pleural fluid, peritoneal fluid, cerebrospinal fluid, tears, urine, saliva, sputum, nipple aspirates, lymph fluid, fluid of the respiratory, intestinal, and genitourinary trances, breast milk, intra-organ system fluid, peritoneal fluid, conditioned media from tissue explant culture, or combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein exomeres are recovered. 
     
     
         4 . The method of  claim 1 , wherein small exosomes are recovered. 
     
     
         5 . The method of  claim 1 , wherein large exosomes are recovered. 
     
     
         6 . The method of  claim 3 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more proteins contained in said exomeres. 
     
     
         7 . The method of  claim 6 , wherein said method is carried out to determine if the subject has cancer by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of PPID, GANAB, MAT1A, CPYD, FAT4, GMPPB, ERP44, CALR, GPD1, BZW1, PFKL, OLFML3, HGD, LGALS3BP, GCLC, PEPD, MTHFD1, PGD, ACTR3, XPNPEP1, UGP2, SNX2, ALDOC, SEPT11, HSPA13, AARS, SERPINH1, CNDP2, PDE5A, AGL, EXT1, IDH1, SERPINC1, RRM1, CKB, HMGCS1, HPD, PSMC4, NPEPPS, CAT, EXT2, CORO1C, B4GAT1, RACK1, MAPRE1, PGM1, PD1A3, ADK, SHMT1, ACO1, GSN, ESD, PPP2R1A, ALDH1L1, OLA1, ACLY, EEF1G, FLNB, PSMD11, ANGPTL3, FERMT3, PYGL, MDH1, and EIFA2. 
     
     
         8 . The method of  claim 4 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more proteins contained in said small exosomes. 
     
     
         9 . The method of  claim 8 , wherein said method is carried out to determine if the subject has cancer by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of TTYH3, FLOT1, FLOT2, TSPAN14, LAMC1, CD63, MVB12A, ZDHHC20, VAMP3, VPS37B, ARRDC1, and TGFBR2. 
     
     
         10 . The method of  claim 5 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more proteins contained in said large exosomes. 
     
     
         11 . The method of  claim 10 , wherein said method is carried out to determine if the subject has cancer by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of SQSTM1, STIP1, HINT1, WASF2, RASA3, EPB41L2, GIPC1, S100A10, MPP6, KIF23, RACGAP1, ANXA5, CASK, DLG1, TJP1, BAG5, TXN, ABI1, ANXA1, CAPG, DB1, S100A6, CHMP2B, CHMP3, ANXA2, MYO1C, ANXA4, SNX12, LIN7C, STXBP3, CEP55, ALCAM, VCL, CHMP1A, FARP1, ACSL4, BA1AP2, SH3GL1, DSTN, LGALS1, CYFIP1, CTNNA1, RAB31, ARF6, SLC1A5, EPS8, FMNL2, PGAM1, CNP, CHMP4B, ANXA3, VPS4B, GNG12, PACSIN3, GLG1, VTA1, LYN, VPS37C, CHMP5, F3, DNAJA1, RHOC, GNA13, CHMP2A, ATP2B1, RDX, ATP1B1, CAPZB, EHD1, DNAJA2, and CTNND1. 
     
     
         12 . The method of  claim 6 , wherein said method is carried out to determine if the subject has melanoma by detecting, higher or lower levels, relative to a standard for subjects not having melanoma, or the presence or absence, of one or more of the proteins selected from the group consisting of IT1H2, IT1H3, H2AFX, PMEL, MAT1A, HPD, ALB, B4GAT1, ARF1, GCLC, HGD, PPP2CB, PAH, AGL, RNPEP, PPID, BZW1, ME1, DPYD, CA6, OLFML3, NPEPPS, PREP, ERP44, RELN, GPD1, GFPT1, CNDP2, PFKL, ALDH8A1, ATP6V1A, ENO2, THBS3, CORO1C, EXT1, CAT, XPNPEP1, PYGL, CALR, and LGALS3BP. 
     
     
         13 . The method of  claim 8 , wherein said method is carried out to determine if the subject has melanoma by detecting, higher or lower levels, relative to a standard for subjects not having melanoma, or the presence or absence, of one or more of the proteins selected from the group consisting of TYRP1, SDCBP, SDCBP, CD63, IGSF8, HSPA8, MLANA, HBA1/HBA2, GPNMB, DCT, HSPA2, HSPA1L, HSPA5, Fv4, PDCD61P, RAB7A, ENV1, CD81, GNB1, SYT4, GNB2, HIST1H2AH, GNAI2, GAPDH, APOE, BC035947, Hist1h2a1, ACTG1, ACTB, GNB4, GNA13, SLC3A2, ACTC1, GNAS, SLC38A2, HIST2H2BF, ATP1A1, TFRC, TMEM176B, VAMP8, TSPAN10, ADGRG1, Hist1h4a, PMEL, UBL3, PPIA, ACTBL2, CD9, BACE2, and TSPAN4. 
     
     
         14 . The method of  claim 10 , wherein said method is carried out to determine if the subject has melanoma by detecting, higher or lower levels, relative to a standard for subjects not having melanoma, or the presence or absence, of one or more of the proteins selected from the group consisting of HSPA8, TYRP1, SDCBP, HSPA2, RPS27A, HSPA1L, MLANA, HSPA5, CD63, IGSF8, GPNMB, Fv4, ENV1, PDCD61P, HSPA1A/HSPA1B, DCT, ACTG1, ACTB, PPIA, SLC3A2, ACTC1, CD81, ITM2C, RAB7A, GNB1, TSPAN4, DNAJA1, GNB2, TFRC, HBA1/HBA2, GNAI2, SYT4, GAPDH, APOE, PMEL, MFGE8, GNB4, GNA13, GNAO1, DNAJA2, ATP1A1, ITGB1, TMEM59, SLC38A2, GNA12, ITM2B, GNAS, HIST1H2AH, LAMP1, and EEF1A1. 
     
     
         15 . The method of  claim 6 , wherein said method is carried out to determine if the subject has breast cancer by detecting, higher or lower levels, relative to a standard for subjects not having breast cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of FGB, HIST2H2AB, COMP, HIST1H2BJ, C7, GSTA5, ENO3, ARF3, SULT1C4, E1F4A2, MAT1A, GNB2, UGDH, AKR1B10, MTHFD1, CTSC, DPP3, RPSA, OTUB1, ALDH8A1, F11, CTPS2, MGAT1, HYH1, LGALSL, GSTM3, GSTM5, PSMC1, F8, PRKAR2B, RPL10A, HNRNPK, SEMA6D, SNX5, IARS, LCP2, ARPC4, PPP6C, PSMD6, PTPRS, TIE1, PSMD8, PABPC4, RPS18, CHAD, IPO5, FABP3, GALNT2, QPCT, STAT5A, SEMA3A, NT5C2, IDE, STAT3, DPYSL3, PDXK, ARF5, PSMD5, GNE, NBEAL2, FHL1, TIMP3, POSTN, MAPRE2, IT1H3, C3, ENO2, PPID, O1T3, CAND1, SEPT2, UBE2N, DPYSL2, CKB, PTGES3, DSTN, PKLR, THBS3, RAP1B, HIST2H2AB, ACTBL2, TUBB2A, F10, CNTN1, HPD, ACE, EML2, HSPA13, TNXB, HEXB, CALR, ADH5, GPX1, CFL2, KRT76, TCP1, COTL1, DYNLL1, HGD, ALDOC, EPRS, GLO1, MAN2A1, FLT4, NAP1L4, RARS, HMGCS1, GANAB, SEPT7, FKBP4, COL12A1, ADSL, AKR1C20, VASN, DDX39B, ME1, COMT, ALDH1A1, EIF4A3, CDH11, PRPS1I3, PNPEP, NPEPPS, SEPT11, CMBL, PSMD1, ACTR1B, PSMD3, GCLC, FAT4, LPL, GPD1L, GCLM, VARS, PHPT1, CACNA2D1, SEPT9, GLRX3, AARS, GMPPB, SNX2, GLOD4, PTPRF, CSAD, PXDN, AGL, DPYD, PRKACB, LARS, PPID, LTA4H, PSMD7, CAPNS1, ETF1, IARS, VPS35, TKFC, HYOU1, PGM2, TKT, HMCN1, CYB5R3, GPS1, UMPS, SND1, RTCB, RPL26, CARM1, PLCG2, P4HA2, CORO6, GMPS, IGSF8, PPP1R7, TIMP3, UXS1, DNM2, MEMO1, RPS3, ARHGD1A, PTGES3, NRP2, RAB1A, HBG2, and YWHAQ. 
     
     
         16 . The method of  claim 8 , wherein said method is carried out to determine if the subject has breast cancer by detecting, higher or lower levels, relative to a standard for subjects not having breast cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of SDCBP, HIST1H2BN, HIST1H2AH, HBA1/HBA2, ITGB1, Hist1h4a, PDCD61P, HIST3H2BB, H2AFX, CD9, CD63, ITGA3, IT1H2, MFGE8, H2AFZ, PTGFRN, Hist1h3b, HSPA8, ACTG1, ACTB, ARRDC1, ACTC1, IT1H3, IGSF8, GSN, TUBA4A, HIST1H1D, TUBA1A, HIST1H1C, THBS1, HSPA2, ENO1, MVB12A, HTRA1, GAPDH, Hist1h1e, VPS28, TSG101, TUBB, TUBB4A, RAP1B, PFN1, CD81, VPS37B, TUBB6, RAP1A, EPCAM, Hist1h1b, PPIA, ADAM10, HBA1, HIST1H2BK, A2M, ED1L3, SDCBP, MFGE8, GSN, HIST2H2AC, HIST1H2AC, H2AFX, ACTB, THBS1, IT1H4, TUBB, TUBB2A, TUBB4B, F10, H2AFZ, TUBB4A, TUBB6, TUBB1, HSPA8, CD9, CD81, GAPDH, PFN1, HIST1H4A, HSP90AA1, HSP90AB1, HSPA2, HIST2H3A, PGK1, THBS2, EEF1A1, GPX3, ITGB1, PPIA, PDCD61P, EEF1A2, FBLN1, ATIC, CPNE8, TLN1, HSPA5, PKM, HIST1H1C, WDR1, RAN, PYGL, and ITGA3. 
     
     
         17 . The method of  claim 10 , wherein said method is carried out to determine if the subject has breast cancer by detecting, higher or lower levels, relative to a standard for subjects not having breast cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of PDCD61P, SDCBP, EHD1, ITGB1, S100A6, ITGA3, CD9, VPS37C, Hist1h4a, RAP1B, CTNNA1, MSN, HIST1H2AH, ITGA2, PTGFRN, ACTG1, HIST1H2BN, Calm1, EPCAM, ITGA6, YWHAE, HSPA1A/HSPA1B, GNB1, SLC3A2, GNB2, EHD2, H2AFX, PPIA, NT5E, VPS4B, GNB4, Cdc42, SLC1A5, GNAI2, CFL1, YWHAH, EEF1A1, YWHAB, Hist1h3b, TSG101, YWHAG, ANXA5, GNA13, F5, H3F3A/H3F3B, CHMP4B, HSPA5, EZR, GAPDH, CD81, ED1L3, HBA1/HBA2, UBC, SDCBP, HSPA8, ITGB1, CD9, HSPA2, ACTC1, ACTB, ACTG1, PDCD61P, AFP, HBG2, ANXA2, ITGA3, HIST1H2BK, GAPDH, CD81, SLC3A2, GNAI2, GNA13, GNAI1, ATP1A1, HIST2H2AC, CPNE8, IST1, PFN1, TUBA4A, H2AFX, TUBA1C, HSPA5, YWHAZ, ENO1, ANXA5, GNAS, DNAJA1, CHMP5, EEF1A1, RHOA, KRT1, CEP55, GNB1, ACTBL2, ITGA2, EPHA2, GNA13, PPIA, RAP1A, and CD59. 
     
     
         18 . The method of  claim 6 , wherein said method is carried out to determine if the subject has pancreatic cancer by detecting, higher or lower levels, relative to a standard for subjects not having pancreatic cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of SULT1E1, PKLR, ENO2, AKR1B1, FH, MGAT2, GPX1, DPP3, SEMA4B, GPD1, CSAD, NCAM1, PCMT1, NARS, THOP1, UMPS, PDE5A, CACNA2D1, TIE1, CDH11, AOX1, F8, GLB1, RPL10A, ACAP2, UXS1, ADSL, BMP1, PSMD3, LANCL1, GLO1, PPP2CA, ESD, PSMD5, FARSB, PAFAH1B1, SNX5, XPO1, MAPRE1, APRT, NEO1, GBA, THBS1, PYGL, THBS2, FAT4, CNTN1, AKR1C20, E1F4A2, ESD, BPGM, VASN, MAT1A, MAT2A, PFKL, CLIC5, HGD, GLOD4, AGL, PLEKHB2, CLSTN1, ST13, CMBL, AKR1E2, PRKAR2A, GPD1, LGALSL, GLA, IL1RAP, GMPPB, PCSK6, SEPT9, PSMC6, FYN, PAFAH1B1, VPS37C, CTNND1, NRBP1, ERP44, SHMT1, DARS, ADSL, GCLM, ALDOC, EPHA4, PEPD, CKB, PCMT1, UGDH, PRKAR1A, and GNAS. 
     
     
         19 . The method of  claim 8 , wherein said method is carried out to determine if the subject has pancreatic cancer by detecting, higher or lower levels, relative to a standard for subjects not having pancreatic cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of SDCBP, PDCD61P, HSPA8, IGSF8, CD9, PTGFRN, ACTC1, LY6E, ACTB, MFGE8, HSPA2, CD81, ITGA3, ITGB1, IT1H2, VPS28, CD63, HTRA1, ENV1, Fv4, GSN, ENO1, ED1L3, MVB12A, IF1TM3, SERPINC1, ACTBL2, TUBA4A, PPIA, HSPA1A/HSPA1B, HSPA5, GAPDH, TSG101, TUBB, PLEKHB2, TUBA1C, TUBB4B, PFN1, GPC1, GJA1, EHD1, GNB2, TSPAN4, GNAI2, SLC3A2, VPS37B, GNA13, RAB7A, EEF1A1, GNAS, ALB, HBA1/HBA2, CD9, UBC, SDCBP, F2, ACTG1, ACTB, CD59, ACTC1, ACTA2, A2M, HIST1H2BK, HIST1H2BJ, HSPA8, TSPAN3, HIST2H2AC, CD55, H3F3A/H3F3B, HIST2H3PS2, PDCD61P, ITGB1, POTEJ, SERINC5, H2AFZ, ARRDC1, CLDN3, NT5E, EPCAM, CDH17, ATP1A1, ALPPL2, HIST2H2AB, ALPP, HSPA2, TSPAN8, MVP, ADAM10, THBS1, VNN1, ITGAV, IGSF8, MYOF, ATP1A2, AHCY, GSN, TSPAN1, PPIA, SDCBP2, and HSPA5. 
     
     
         20 . The method of  claim 10 , wherein said method is carried out to determine if the subject has pancreatic cancer by detecting, higher or lower levels, relative to a standard for subjects not having pancreatic cancer, or the presence or absence, of one or more of the proteins selected from the group consisting of ACTC1, ACTG1, ACTB, MFGE8, ITGB1, HSPA8, ITGA3, SDCBP, GAPDH, LGALS1, ENV1, Fv4, YWHAZ, PPIA, GNB1, GNAI2, GNB2, ACTBL2, GNA13, CFL1, Marcks, GNAS, EEF1A1, ENO1, BSG, Calm1, S100A4, MSN, EZR, RDX, PTGFRN, PKM, SLC3A2, HBA1/HBA2, ED1L3, GNA13, RHOA, RHOC, S100A6, YWHAE, ALDOA, PDCD61P, PFN1, HSP90AB1, YWHAQ, ANXA1, ANXA2, ATP1A1, ITGA6, UBC, HBA1/HBA2, CD9, ACTG1, ACTB, CD59, MVP, SDCBP, ACTC1, ACTA2, HIST1H2BK, HIST2H2AC, ALB, HSPA8, HIST1H2BJ, CD55, H3F3A, TSPAN3, HIST2H3PS2, POTEJ, DPP4, NT5E, EPCAM, VNN1, H2AFZ, ITGB1, ALPPL2, HIST2H2AB, ATP1A1, ALPP, IST1, PDCD61P, MUC13, ANXA11, HSPA2, CDH17, GPA33, ANXA2, S100A6, ATP1A2, PPIA, EGFR, TSPAN8, MYOF, GNAI1, GNAI2, GNA13, S100A4, CLDN3, and A2M. 
     
     
         21 . The method of  claim 1 , wherein said one or more reagents suitable for detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more proteins contained in said exomeres, small exosomes, or large exosomes measure protein expression level. 
     
     
         22 . The method of  claim 3 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more N-glycans contained in said exomeres. 
     
     
         23 . The method of  claim 22 , wherein said one or more N-glycans are selected from the group consisting of N-glycan (Fucose)+GlcNAcβ1-6(GlcNAcβ1-2)Manα1-6(GlcNA β1-4(GlcNAcβ1-2)Manα1-3)Manβ1-4GlcNAcβ1-4(Fucα1-6)GlcNAcβ1-Asn and N-glycan (Fucose)+Neu5Acα2-8Neu5Acα2-3Galβ1-3/4GlcNAcβ1-2Manα1-3(Manα1-3(Manα1-6))Manα1-6)Manβ1-4GlcNAcβ1-4GlcNAcβ1-Asn. 
     
     
         24 . The method of  claim 4 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more N-glycans contained in said small exosomes. 
     
     
         25 . The method of  claim 5 , wherein said contacting is carried out by detecting, higher or lower levels relative to a standard for subjects not having cancer, or the presence or absence, of one or more N-glycans contained in said large exosomes. 
     
     
         26 . The method of  claim 3 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more lipids contained in said exomeres. 
     
     
         27 .- 28 . (canceled) 
     
     
         29 . The method of  claim 4 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more lipids contained in said small exosomes. 
     
     
         30 .- 31 . (canceled) 
     
     
         32 . The method of  claim 5 , wherein said contacting is carried out by detecting, higher or lower levels, relative to a standard for subjects not having cancer, or the presence or absence, of one or more lipids contained in said large exosomes. 
     
     
         33 .- 34 . (canceled) 
     
     
         35 . The method of  claim 1 , wherein said contacting is carried out by detecting the presence or absence, relative to a standard for subjects not having cancer, of one or more genetic mutations in nucleic acid molecules associated with cancer and contained in said exomeres, said small exosomes, or said large exosomes. 
     
     
         36 .- 37 . (canceled) 
     
     
         38 . The method of  claim 1  further comprising:
 selecting a suitable cancer therapeutic based on said diagnosing and administering the selected cancer therapeutic to said selected subject. 
 
     
     
         39 . A method of prognosing cancer in a subject, said method comprising:
 selecting a subject having cancer;   obtaining, from the selected subject, a population of either exomeres having a diameter of less than 50 nm, small exosomes having a diameter of 60-80 nm, or large exosomes having a diameter of 90-120 nm;   recovering the exomeres, small exosomes, or large exosomes from the sample;   contacting the exomeres, small exosomes, or large exosomes or portions thereof with one or more reagents suitable to detect: (1) higher or lower levels, relative to a standard or to the level in a prior sample obtained from the subject, or the presence or absence, of one or more proteins contained in said exomeres, small exosomes, or large exosomes, (2) higher or lower levels, relative to a standard or to the level in a prior sample obtained from the subject, or the presence or absence, of one or more N-glycans contained in said exomeres, small exosomes, or large exosomes, (3) higher or lower levels, relative to a standard or to the level in a prior sample obtained from the subject, or the presence or absence, of one or more lipids contained in said exomeres, small exosomes, or large exosomes, (4) the presence or absence of one or more genetic mutations in nucleic acid molecules associated with cancer and contained in said exomeres, small exosomes, or large exosomes, or (5) combinations thereof, and   prognosing the cancer based on said contacting.   
     
     
         40 . A method of managing treatment of a subject having cancer, said method comprising:
 selecting a subject undergoing treatment for cancer;   obtaining, from the selected subject, a population of either exomeres having a diameter of less than 50 nm, small exosomes having a diameter of 60-80 nm, or large exosomes having a diameter of 90-120 nm;   recovering the exomeres, small exosomes, or large exosomes from the sample;   contacting the exomeres, small exosomes, or large exosomes or portions thereof with one or more reagents suitable to detect: (1) higher or lower levels, relative to a standard or to the level in a prior sample obtained from the subject, or the presence or absence, of one or more proteins contained in said exomeres, small exosomes, or large exosomes, (2) higher or lower levels, relative to a standard or to the level in a prior sample obtained from the subject, or the presence or absence, of one or more N-glycans contained in said exomeres, small exosomes, or large exosomes, (3) higher or lower levels, relative to a standard or to the level in a prior sample obtained from the subject, or the presence or absence, of one or more lipids contained in said exomeres, small exosomes, or large exosomes, (4) the presence or absence of one or more genetic mutations in nucleic acid molecules associated with cancer and contained in exomeres, small exosomes, or large exosomes, or (5) combinations thereof, and   modifying said treatment, as necessary, based on said contacting.   
     
     
         41 .- 78 . (canceled) 
     
     
         79 . A kit suitable for diagnosing cancer, said kit comprising:
 one or more reagents suitable to detect: (1) higher or lower levels, relative to a standard or to a sample from a subject, or the presence or absence, of one or more proteins contained in exomeres, small exosomes, or large exosomes, (2) higher or lower levels, relative to a standard or to a sample from a subject, or the presence or absence, of one or more N-glycans contained in exomeres, small exosomes, or large exosomes, (3) higher or lower levels, relative to a standard or to a sample from a subject, or the presence or absence, of one or more lipids contained in exomeres, small exosomes, or large exosomes, (4) the presence or absence of one or more genetic mutations in nucleic acid molecules associated with cancer and contained in exomeres, small exosomes, or large exosomes, or (5) combinations thereof, wherein said exomeres have a diameter of less than 50 nm, small exosomes have a diameter of 60 to 80 nm and said large exosomes have a diameter of 90 to 120 nm.   
     
     
         80 .- 111 . (canceled)