Repurposing drugs for non-small cell lung cancer

A method for treating non-small cell lung cancer (NSCLC) in a subject, comprising:

• (a) assaying a sample from the subject for expression levels of COPA, CSE1L, EIF2AK3, FOSL1, LSM3, MCM5, PMPCB, POLR1B, POLR2F, PSMD11, RPL32, RPS18, SNRPE, SPP1, IFITM3, ATP1B4, PRRX1, FUT7, POF1B, ZNF671, ZBED2, C10orf10, ERH, KLHL6, SERPING1, TRIM29, CCR2, TNFSF12-TNFSF13, ATP1B4, PRDM1, RGS17, CD80, ARK1C1, DEFB103A, CSPP1, AKR1C2, DSG3, PRDM1, ABCA13, ARSE, PTAFR, ZEB1, ERH, F13A1, KLHL6, PRRX1, GPX2, LAIR1, TRIM22, PTAFR, RAB25, ESRP1, SERPINB5, KLHL6, CD80, SH2D1A, CD27, TGM5, CD274, HLA-F, LY75, F13A1, CTSH, CPNE8, ARSE, HLA-DMB, SLC39A8, HNMT, CTSH, CDH3, HNMT, ABCA13, F13A1, DUSP2, HLA-DRB1, TIGIT, TNIP3, ANAPC5, OAS1, VCP, IL2RA, LMNA, PPP2R1A, TNIP3, CCND2, TSC22D3, HRH1, CCT3, EWSR1, TUBA1B, HSD17B13, MAP4, HRH1, CD74, HLA-DRA, HSD17B13, EXOC4, GBP4, TSC22D3, or a combination thereof;
• and
• (b1) detecting elevated levels of DUSP2, VCP, IL2RA, LMNA, CCT3, PPP2R1A, POF1B, CD274, HLA-F, LY75, PRRX1, and/or F13A1, detecting reduced levels of PSMD11, ANAPC5, OAS1, FUT7, ZNF671, ZBED2, C10orf10, CTSH, and/or TRIM29, or a combination thereof, in a sample from the subject, and treating the subject with cisplatin;
• (b2) detecting elevated levels of RPS18, PMPCB, TNIP3, IL2RA, CCND2, GBP4, ERH, KLHL6, AKR1C1, AKR1C2, SERPINB5, and/or POLR1B, detecting reduced levels of IFITM3, C10orf10, SERING1, PSMD11, LMNA, PPP2R1A, TUBA1B, CPNE8, and/or EIF2AK3, or a combination thereof, and treating the subject with docetaxel;
• (b3) detecting elevated levels of RPL32, TSC22D3, CCT3, VCP, KLHL6, TRIM29, IFITM3, SERPINB5, PRDM1, RGS17, CD80, AKR1C1, AKR1C2, DEFB103A, CSPP1, ARSE, HLA-DMB, TRIM22, POF1B, LSM3, and/or POLR2F, detecting reduced levels of CSE1L, DUSP2, HRH1, LMNA, LY75, TGM5, F13A1, IFITM3, CCR2, TNFSF12-TNFSF13, ATP1B4, SERPING1, DSG3, and/or FOSL1, or a combination thereof, and treating the subject with erlotinib;
• (b4) detecting elevated levels of CCT3, EWSR1, TUBA1B, VCP, HSD17B13, LMNA, PSMD11, PRDM1, ATP1B4, SERPING1, ABCA13, HLA-F, ABCA13, and/or SERPINB5, detecting reduced levels of TGM5, TRIM29, and/or ARSE, or a combination thereof, and treating the subject with etoposide;
• (b5) detecting elevated levels of CCND2, CCT3, CCT3, HLA-DRA, TSC22D3, CCT3, DEFB103A, PTAFR, CSPP1, KLHL6, TRIM29, and/or SLC39A8, detecting reduced levels of COPA, OAS1, VCP, HSD17B13, LMNA, MAP4, TUBA1B, HRH1, HSD17B13, ZEB1, ERH, F13A1, RGS17, ATP1B4, PRRX1, SERPING1, and/or ARSE, or a combination thereof, and treating the subject with gefitinib;
• (b6) detecting elevated levels of CCT3, CD74, DUSP2, HLA-DRA, TIGIT, LMNA, VCP, ARSE, GPX2, RGS17, LAIR1, TRIM22, TGM5, CTSH, HLA-F, SERPINB5, CDH3, HNMT, SPP1, and/or MCM5, detecting reduced levels of PSMC3, EXOC4, SERPING1, ARSE, C10orf10, ABCA13, AKR1C2, GPX2, C10orf10, and/or RPS18, or a combination thereof, and treating the subject with gemcitabine;
• (b7) detecting elevated levels of DUSP2, VCP, OAS1, TNIP3, PTAFR, TRIM29, RAB25, ESRP1, SERPINB5, KLHL6, CD80, CD27, CDH3, PRRX1, PMPCB, RPS18, POLR1, and/or LY75, detecting reduced levels of PSMD11, PPP2R1A, HSD17B13, CD74, HLA-DRA, TUBA1B, SH2D1A, C10orf10, HLA-F, SLC39A8, CTSH, and/or TRIM29, or a combination thereof, and treating the subject with paclitaxel;
• (b8) detecting elevated levels of CCT3, DUSP2, ANAPC5, HRH1, and/or RPS18, detecting reduced levels of SH2D1A, or a combination thereof, and treating the subject with pemetrexed;
• (b9) detecting elevated levels of FUT, VCP, CCT3, DUSP2, CCND2,, SERPINB5, AKR1C2, AKR1C1, F13A1, HLA-F, and/or POLR2F, detecting reduced levels of CSE1L, EXOC4, HRH1, LMNA, TNFSF12-TNFSF13, DSG3, SNRPE, and/or CTSH, or a combination thereof, and treating the subject with vinorelbine;
• or
• (b10) detecting elevated levels of DUSP2, TIGIT, TGM5, and/or IFITM3, detecting reduced levels of HLA-DRB1, TNIP3, ATP1B4, and/or PRRX1, or a combination thereof, and treating the subject with carboplatin.

A system, comprising:

• a computing device comprising a processor and memory;
• and
• an application to generate Boolean implication networks when compiled with the computing device, the application comprising machine readable instructions stored in the memory that, when executed by the processor, cause the computing device to at least:
• generate one or more multi-omics networks from patient cohort information based upon one or more Boolean implication networks;
• identify prognostic genes based upon the one or more multi-omics networks and patient gene expression profiles and associated clinical information;
• identify proliferation genes based upon the one or more multi-omics networks and screening results in cell lines;
• delineating a final multi-omics network based upon identified prognostic and proliferation genes;
• and
• identifying a repurposing drug based upon the final multi-omics network.