Enhanced antitumor activity of an anti-5T4 antibody-drug conjugate in combination with PI3K/mTOR inhibitors or taxanes

Clinical Cancer Research

Volumn 22, Issue 2, 2016, Pages 383-394

  Shor, Boris ^a   Kahler, Jennifer ^a   Dougher, Maureen ^a   Xu, Jane ^a   Mack, Michelle ^a   Rosfjord, Ed ^a   Wang, Fang ^a   Melamud, Eugene ^a   Sapra, Puja ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; AURISTATIN 5T4 ANTIBODY CONJUGATE; GEDATOLISIB; GLYCOGEN SYNTHASE KINASE; MESSENGER RNA; PACLITAXEL; PROTEIN KINASE B; SOBLIDOTIN; UNCLASSIFIED DRUG; AMINOBENZOIC ACID DERIVATIVE; ANTIBODY CONJUGATE; AURISTATIN; MEMBRANE PROTEIN; MONOCLONAL ANTIBODY; MTOR PROTEIN, HUMAN; OLIGOPEPTIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE INHIBITOR; TARGET OF RAPAMYCIN KINASE; TAXOID; TROPHOBLASTIC GLYCOPROTEIN 5T4, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CELL VIABILITY; CONTROLLED STUDY; DRUG CONJUGATION; DRUG MECHANISM; DRUG POTENTIATION; FEMALE; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; IN VITRO STUDY; LUNG TUMOR; MITOSIS INDEX; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; RNA TRANSLATION; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; DRUG EFFECTS; DRUG INTERACTION; DRUG SCREENING; HT-29 CELL LINE; METABOLISM; NUDE MOUSE; PROCEDURES; PROTEOMICS; TUMOR CELL LINE;

AMINOBENZOATES; ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; DRUG INTERACTIONS; FEMALE; HT29 CELLS; HUMANS; IMMUNOCONJUGATES; MEMBRANE GLYCOPROTEINS; MICE; MICE, NUDE; OLIGOPEPTIDES; PACLITAXEL; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTEOMICS; RNA, MESSENGER; TAXOIDS; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84958960545     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-1166     Document Type: Article

References (45)

1. Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 2013;31:1157-63.
2. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783-91.
3. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: Results of a phase II study. J Clin Oncol 2012;30:2190-6.
4. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 2012;30:2183-9.
5. Maderna A, Doroski M, Subramanyam C, Porte A, Leverett CA, Vetelino BC, et al. Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications. J Med Chem 2014;57:10527-43.
6. Doronina SO, Toki BE, Torgov MY, Mendelsohn BA, Cerveny CG, Chace DF, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 2003;21:778-84.
7. Sapra P, DamelinM,Dijoseph J,Marquette K,Geles KG, Golas J, et al. Longterm tumor regression induced by an antibody-drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells. Mol Cancer Ther 2013;12:38-47.
8. Fruman DA, Rommel C. PI3K and cancer: Lessons, challenges and opportunities. Nat Rev Drug Discov 2014;13:140-56.
9. Chandarlapaty S, Sakr RA, Giri D, Patil S, Heguy A, Morrow M, et al. Frequentmutational activation of the PI3K-AKT pathway in trastuzumabresistant breast cancer. Clin Cancer Res 2012;18:6784-91.
10. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004; 6:117-27.
11. Jeannot V, Busser B, Brambilla E, Wislez M, Robin B, Cadranel J, et al. The PI3K/AKT pathway promotes gefitinib resistance in mutant KRAS lung adenocarcinoma by a deacetylase-dependent mechanism. Int J Cancer 2014;134:2560-71.
12. Andre F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014;15:580-91.
13. Sampath D, Fields C, Li G, Prior W, Parsons K, Friedman L, et al. Abstract S3-6: Combination therapy of the novel PI3K inhibitor GDC-0941 and dual PI3K/mTOR inhibitor GDC-0980 with trastuzumab-DM1 antibody drug conjugate enhances anti-tumor activity in preclinical breast cancer models in vitro and in vivo. Cancer Res 2011;70:S3-6.
14. Hudis C, Swanton C, Janjigian YY, Lee R, Sutherland S, Lehman R, et al. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors. Breast Cancer Res 2013;15:R110.
15. Hurvitz SA, Dalenc F, Campone M, O'Regan RM, Tjan-Heijnen VC, Gligorov J, et al. A phase 2 study of everolimus combined with trastuzumab and paclitaxel in patients with HER2-overexpressing advanced breast cancer that progressed during prior trastuzumab and taxane therapy. Breast Cancer Res Treat 2013;141:437-46.
16. Mallon R, Feldberg LR, Lucas J, Chaudhary I, Dehnhardt C, Santos ED, et al. Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor. Clin Cancer Res 2011;17:3193-203.
17. ShapiroGI, Bell-McGuinn KM,Molina JR, Bendell J, Spicer J, Kwak EL, et al. First-in-human study of PF-05212384 (PKI-587), a small-molecule, intravenous, dual inhibitor of PI3K and mTOR in patients with advanced cancer. Clin Cancer Res 2015;21:1888-95.
18. Yared JA, Tkaczuk KH. Update on taxane development: New analogs and new formulations. Drug Des Devel Ther 2012;6:371-84.
19. Joshi M, Liu X, Belani CP. Taxanes, past, present, and future impact on nonsmall cell lung cancer. Anticancer Drugs 2014;25:571-83.
20. Schiff PB, Horwitz SB. Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A 1980;77:1561-5.
21. Perez EA. Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Mol Cancer Ther 2009;8:2086-95.
22. Gudena V, Montero AJ, Gluck S. Gemcitabine and taxanes in metastatic breast cancer: A systematic review. Ther Clin Risk Manag 2008;4:1157-64.
23. Boghaert ER, Sridharan L, Khandke KM, Armellino D, Ryan MG, Myers K, et al. The oncofetal protein, 5T4, is a suitable target for antibodyguided anti-cancer chemotherapy with calicheamicin. Int J Oncol 2008; 32:221-34.
24. Damelin M, Geles KG, Follettie MT, Yuan P, Baxter M, Golas J, et al. Delineation of a cellular hierarchy in lung cancer reveals an oncofetal antigen expressed on tumor-initiating cells. Cancer Res 2011;71:4236-46.
25. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010;70:440-6.
26. Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 2003; 161:267-80.
27. VanderPorten EC, Taverna P, Hogan JN, Ballinger MD, Flanagan WM, Fucini RV. The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model. Mol Cancer Ther 2009;8:930-9.
28. Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 2012;485:109-13.
29. Pelletier J, Graff J, Ruggero D, Sonenberg N. Targeting the eIF4F translation initiation complex: A critical nexus for cancer development. Cancer Res 2015;75:250-63.
30. Bai RL, Pettit GR, Hamel E. Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. J Biol Chem 1990;265:17141-9.
31. Asnaghi L, Calastretti A, Bevilacqua A, D'Agnano I, Gatti G, Canti G, et al. Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt. Oncogene 2004;23:5781-91.
32. Franz-Wachtel M, Eisler SA, Krug K, Wahl S, Carpy A, Nordheim A, et al. Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 2012; 11:160-70.
33. Nagano K, Shinkawa T, Mutoh H, Kondoh O, Morimoto S, Inomata N, et al. Phosphoproteomic analysis of distinct tumor cell lines in response to nocodazole treatment. Proteomics 2009;9:2861-74.
34. Kim S, Coulombe PA. Emerging role for the cytoskeleton as an organizer and regulator of translation. Nat Rev Mol Cell Biol 2010;11:75-81.
35. Coldwell MJ, Cowan JL, Vlasak M, Mead A, Willett M, Perry LS, et al. Phosphorylation of eIF4GII and 4E-BP1 in response to nocodazole treatment: A reappraisal of translation initiation during mitosis. Cell Cycle 2013;12:3615-28.
36. Blower MD, Feric E, Weis K, Heald R. Genome-wide analysis demonstrates conserved localization of messenger RNAs to mitotic microtubules. J Cell Biol 2007;179:1365-73.
37. Lecuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T, Cerovina T, et al. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 2007;131:174-87.
38. Sharp JA, Plant JJ, Ohsumi TK, Borowsky M, Blower MD. Functional analysis of the microtubule-interacting transcriptome. Mol Biol Cell 2011;22:4312-23.
39. Skop AR, Liu H, Yates J 3rd, Meyer BJ, Heald R. Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. Science 2004;305:61-6.
40. Jang CY, Kim HD, Zhang X, Chang JS, Kim J. Ribosomal protein S3 localizes on themitotic spindle and functions as amicrotubule associated protein in mitosis. Biochem Biophys Res Commun 2012;429:57-62.
41. Wallin JJ, Guan J, Prior WW, Lee LB, Berry L, Belmont LD, et al. GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo. Clin Cancer Res 2012;18:3901-11.
42. Krop I, Wolff A, Winer E, Miller K, Park B, Ware J, et al. Abstract P6-15-02: A phase Ib study evaluating safety, tolerability, pharmacokinetics (PK), and activity of the phosphoinositide-3 kinase (PI3K) inhibitor GDC-0941 in combination with trastuzumab-MCC-DM1 (T-DM1) in patients with advanced HER2-positive breast cancer. Cancer Res 2010;70:P6-15-02.
43. Martin M, Dewar J,Albanell J, Limentani S, Chang J, Strasak A, et al. Abstract P4-12-07: Neoadjuvant trastuzumab emtansine and docetaxel, with or without pertuzumab, in patients with HER2-positive early-stage breast cancer: Results from a phase 1b/2a study. Cancer Res 2013;73:P4-12-07.
44. Ansell SM, Younes A, Connors JM, Gallamini A, Kim WS, Friedberg JW, et al. Phase 3 study of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as front-line treatment for advanced classical Hodgkin lymphoma (HL): Echelon-1 study. ASCO Meeting Abstracts 2014;32:TPS8613.
45. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013;41:D808-15.