Trials From Bernards Lab

Clinical trials that have emerged from Bernards laboratory research:

A total of 14 clinical trials (including two global phase 3 studies) have emerged from my research, highlighting the potential societal benefit of my research:

  1. NCT01719380: Encorafenib and cetuximab with or without BYL719 BRAF mutant metastatic CRC.

  2. NCT01750918: Dabrafenib and trametinib plus panitumumab in BRAF mutant metastatic CRC.

  3. NCT01791309: Vemurafenib and panitumumab in BRAF mutant metastatic CRC.

  4. NCT02039336: PD-0325901 and dacomitinib in advanced KRAS mutant cancers.

  5. NCT02230553: Trametinib and lapatinib in advanced KRAS mutant cancers.

  6. NCT02450656: Selumetinib and afatinib in advanced KRAS mutant cancers.

  7. NCT02164916: Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant

    Metastatic Colorectal Cancer.

  8. NCT02928224: BEACON: (Binimetinib, Encorafenib And Cetuximab Combined to treat BRAF-

    mutant Colorectal Cancer) trial, a randomized, global Phase 3 clinical trial).

  9. NCT02836548: HDAC Inhibitor Vorinostat in Resistant BRAF V600 Mutated Advanced

    Melanoma.

  10. NCT00433589: Genetic Testing or Clinical Assessment in Determining the Need for

    Chemotherapy in Women With Breast Cancer That Involves No More Than 3 Lymph Nodes

    (MINDACT).

  11. NCT03147040: "AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular

    Breast Cancer (GELATO)"

  12. NCT02982694: Study With Atezolizumab Plus Bevacizumab in Patients With Chemotherapy

    Resistant, MSI-like, Colorectal Cancer

  13. NCT03470350: Galunisertib and Capecitabine in Advanced Resistant TGF-beta Activated

    Colorectal Cancer

  14. NCT03482362: Vinorelbine in Advanced BRAF-like Colon Cancer.

Trial numbers 1, 2, 3, 7 and 8 are based on publication:
Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R. L., Bardelli, A. & Bernards, R. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100-103, (2012).

Trials 4, 5 and 6 are based on publication:
Sun, C., Hobor, S., Bertotti, A., Zecchin, D., Huang, S., Galimi, F., Cottino, F., Prahallad, A., Grernrum, W., Tzani, A., Schlicker, A., Wessels, L.F.A., Smit, E.F., Thunnissen, E., Halonen, P., Lieftink, C., Beijersbergen, R.L., Di Nicolantonio, F., Bardelli, A Trusolino, L., and Bernards, R. (2014). Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3. Cell Rep. 7, 86-93.

Trial 9 is based on manuscript:
Wang, L., Leite de Oliveira, R., Huijberts, S., Bosdriesz, E., Pencheva, N., Brunen, D., Bosma, A., Zevenhoven, J., de Vries, T., Horlings, H., Nuijen, B., Beijnen, J.H., Schellens, J.H.M. and Bernards, R. (2018). An acquired vulnerability of drug resistant melanoma with therapeutic potential. Cell, 173, 1413-1425.

Trial 10 is based on manuscript:
van de Vijver, M. J., He, Y. D., van't Veer, L. J., Dai, H., Hart, A. A., Voskuil, D. W., Schreiber, G. J., Peterse, J. L., Roberts, C., Marton, M. J., Parrish, M., Atsma, D., Witteveen, A., Glas, A., Delahaye, L., van der Velde, T., Bartelink, H., Rodenhuis, S., Rutgers, E. T., Friend, S. H. & Bernards, R. (2002). A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347, 1999- 2009.

Trial 11 is based on manuscript:
Michaut, M., Chin, S-F., Majewski, I., Severson, T.M., Bismeijer, T, de Koning, L., Peeters, J.K., Schouten, P.C., Rueda, O.M., Bosma, A.J., Tarrant, F., Fan, Y., He, B., Xue, Z., Mittempergher, L., Kluin, R., Heijmans, J., Snel, M., Pereira, B., Schlicker, A., Provenzano, E., Raza Ali, H., Gaber, A., O’Hurley, G., Sammut, S.J., Bardwell, H.A., Barbet, A.S., Bard, F., Lecerf, C., Vis, D.J., Benes, C.H., McDermott, U., Garnett, M.J., Simon, I.M., Jirström, K., Dubois, T., Linn, S., Gallagher, W.M., Wessels, L.F.A., Caldas, C., & Bernards, R (2016). Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer. Sci Rep.6, 18517.

Trial 12 is based on manuscript:
Tian, S., Roepman, P., Popovici, V., Michaut, M., Majewski, I., Salazar, R., Santos, C., Rosenberg, R., Nitsche, U., Mesker, W.E., Bruin, S., Tejpar, S., Delorenzi, M., Bernards, R., and Simon, I. (2012). A robust genomic signature for detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency. J. Pathol. 228, 586-595.

Trial 13 is based on manuscript:
Huang, S., Hölzel, M., Knijnenburg, T., Schlicker, A., Roepman, P., McDermott, U., Garnett, M., Grernrum, W., Sun, C., Prahallad, A., Groenendijk, F.H., Mittempergher, L., Nijkamp, W., Neefjes, J., Salazar, R., ten Dijke, P., Uramoto, H., Tanaka, F., Beijersbergen, R.L., Wessels, L. F. A., and Bernards, R. (2012). MED12 controls the response to multiple targeted cancer drugs through direct regulation of TGF beta receptor signaling. Cell 151, 937-950.

Trial 14 is based on manuscript:
Vecchione, L., Gambino, V., Raaijmakers, J., Schlicker, A., Fumagalli, A., Russo, M., Villanueva, A., Beerling, E., Bartolini, A., Mollevi, D.G., El-Murr, N., Chiron, M., Calvet, L., Nicolazzi, C., Combeau, C., Henry, C., Simon, I.M., Tian, S., in ‘t Veld, S., D’ario, G., Mainardi, S., Beijersbergen, R.L., Lieftink, C., Rumpf-Kienzl, C., Delorenzi, M., Wessels, L., Salazar, R., Di Nicolantonio, F., Bardelli, A., van Rheenen, J., Medema, R., Tejpar, S., and Bernards, R. (2016). A vulnerability of a subset of colon cancers with potential clinical utility. Cell, 165, 317-330.

High-Throughput Functional Genetic and Compound Screens Identify Targets for Senescence Induction in Cancer

High-Throughput Functional Genetic and Compound Screens Identify Targets for Senescence Induction in Cancer.

Wang L1, Leite de Oliveira R1, Wang C1, Fernandes Neto JM1, Mainardi S1, Evers B1, Lieftink C1, Morris B1, Jochems F1, Willemsen L1, Beijersbergen RL1, Bernards R2.

Author information

Abstract

Senescence is a proliferation arrest that can result from a variety of stresses. Cancer cells can also undergo senescence, but the stresses that provoke cancer cells to undergo senescence are unclear. Here, we use both functional genetic and compound screens in cancer cells harboring a reporter that is activated during senescence to find targets that induce senescence. We show that suppression of the SWI/SNF component SMARCB1 induces senescence in melanoma through strong activation of the MAP kinase pathway. From the compound screen, we identified multiple aurora kinase inhibitors as potent inducers of senescence in RAS mutant lung cancer. Senescent melanoma and lung cancer cells acquire sensitivity to the BCL2 family inhibitor ABT263. We propose a one-two punch approach for the treatment of cancer in which a drug is first used to induce senescence in cancer cells and a second drug is then used to kill senescent cancer cells.

https://www.ncbi.nlm.nih.gov/pubmed/29045843