Table 2.
Inhibitory agents targeting deregulated signaling elements involved in sustained growth, survival, and drug resistance of cancer cells
| Targeted signaling element | Name of inhibitory agent |
|---|---|
| Growth and survival signaling | |
| EGFR family member inhibitors | |
| Anti-EGFR (erbB1) antibody | mAb-C225, IMC-C225 |
| Anti-EGF antibody | ABX-EGF |
| Antisense oligonucleotide | As-EGFR, As-EGF, As-TGF-α |
| EGFR-TKI | AG1478, gefitinib, erlotinib, EKB-569 |
| Anti-erbB2 antibody | Trastuzumab |
| EGFR-ErbB2-TKI | PKI-166, TAK165, GW572017 (lapatinib) |
| erbB1, erbB2, erbB3, erbB4-TKI | CI1033 |
| EGFR/VEGFR-TKI | AEE788, ZD6474 |
| Other growth factor signaling inhibitors | |
| Hedgehog signaling inhibitor | SMO inhibitor cyclopamine, anti-SHH antibody |
| Wnt signaling inhibitor | Anti-Wnt antibody, WIF-1 |
| Notch signaling inhibitor | γ-secretase inhibitor |
| IGF-1R signaling inhibitor | Adenovirus-IGF-1r/dn, anti-IGF-1R antibody (A12), IGF-1R-TKI (NVP-AEW541) |
| BCR-ABL-TKI | Imatinib mesylate (ST1571), dasatinib, nilotinib |
| Src-family and ABL-TKI | PD180970 |
| Src-family-TKI | CGP-76030 |
| Hormonal signaling inhibitors | |
| AR | Bicalutamide, flutamide |
| ER | Tamoxifen, raloxifen |
| Apoptotic signaling activators | |
| Ceramide generation activator | Docetaxel, paclitaxel, etoposide, doxorubicin, gefitinib, |
| Ceramide synthase activator | PSC833 |
| Ceramidase inhibitor | N-oleoylethanolamine (OE), LCL204, B13, D-e-MAPP |
| GCS inhibitor | D,L-threo-PPMP (PDMP), PPMP, tamoxifen |
| Sphingosine kinase-1 inhibitor | N,N-dimethylsphingosine (DMS), F-12509a |
| Bcl-2 inhibitor | As-Bcl-2, ABT-737 |
| PI3K inhibitor | LY294002, rapamycin, CCI-779 |
| NF-κB inhibitor | IκBα inhibitor, sulfasalazine, bortezomib (PS-341) |
| COX-2 inhibitor | NS-398, etodolax, celecoxib, rofecoxib |
| VEGFR inhibitor | Anti-VEGFR-antibody, SU5416 |
| Drug resistance signaling inhibitors | |
| ABC transporter inhibitors | |
| P-gp/MDR1/ABCB1 | UIC2 monoclonal antibody, antisense oligodeoxynucleotide verapamil, dexverapamil, cyclosporin A, valspodar (PSC-833), quinidine, cinchonine, tamoxifen, toremifene, VX-710 and GF-120918, retinoid X receptor-selective agonist bexarotene (LGD1069, Targretin), dofequidar fumarate, MS-209, VX-710, flavonoids, gefitinib, CI1033 |
| MRP1/ABCC1 | Anti-MRP1 antibody, NSAIDs (indomethacin, sulindac, tolmetin, acemetacin, zomepirac, mefenamic acid), quinidine, MS-209, VX-710, flavonoids |
| BCRP/ABCG2 | Flavonoids, tamoxifen derivatives, gefitinib, C11033, Prazosin |
| Organic cation transporter OCT-1 inhibitor | |
| Drug resistance signaling inhibitor | |
| EGFR-TKI-DR | IGF-1R inhibitor |
| AR/anti-androgen-DR | EGFR inhibitor (gefitinib) |
| ERα/anti-estrogen-DR | EGFR inhibitor (gefitinib), erbB2 inhibitor |
ABC, ATP-binding cassette; AR, androgen receptor, BCRP, breast cancer resistance protein; COX, cyclooxygenase; D-e-MAPP, D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ER, estrogen receptor; GCS, glucosylceramide synthase; IGF-1R, insulin-like growth factor-1 receptor; IκBα, inhibitor κBα; mAb, monoclonal antibody; MDR1, multidrug resistance 1; MRP1, multidrug resistance-associated protein 1; NF-κB, nuclear factor-κB; NSAIDs, non-steroidal anti-inflammatory drugs; OCT-1, organic cation transporter- 1; P-gp, P-glycoprotein; PI3K, phosphoinositide-3 kinase; SHH, sonic hedgehog; SMO, smoothened; TKI, tyrosine kinase inhibitor; VEGFR, vascular epidermal growth factor receptor; WIF-1, Wnt inhibitory factor-1; Wnt, wingless.