Cancer Institute

Profile picture of Martijn Molkema
Principal Investigator

M.P.J.K. (Martijn) Lolkema, MD

Principal investigator

  • Department
  • Medical oncology
  • Focus area
  • Large scale genomic analyses of metastatic cancer tissues, translational biomarker studies in urogenital cancers and early phase drug development in oncology
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About

Introduction

My research efforts are divided among 3 themes: 

  • Large scale genomic analyses of metastatic cancer tissues 
  • Translational biomarker studies in urogenital cancers 
  • Early phase drug development in oncology

Field(s) of expertise

Genomics of Metastatic Cancer

I have been involved in the Center for Personalized Cancer Treatment since 2010 and this dutch national project where we collected whole genome sequencing data on over 3000 patients is the foundation for many of the studies we perform.

Translational Biomarker Studies in Urogenital Cancers

In collaboration with the lab of translational genomics and experimental urology we perform several studies looking at both tissue based and blood based biomarkers to predict the outcome of treatments and optimize patient selection.

Early Phase Drug Development

In our early phase drug unit we perform many early phase trials in collaboration with pharmaceutical companies. We also perform investigator driven trials together with the pharmacology unit. Finally, our unit performs several studies to understand how we can best inform and select patients that participate in these studies."

Education and career

Martijn Lolkema completed an MD/PhD program in 2008 and received a Dutch Cancer Foundation award to receive additional research training abroad. He visited the UK to perform research on drug development (Royal Marsden Hospital) and translational research using model systems such as genetically engineered mice (Cambridge Research Institute).

In 2010 he started is first position at the UMC Utrecht focussing on genomics in cancer, translational studies in pancreatic cancer and early phase srug development, vchairing the phase I unit.

In 2014 Dr. Lolkema joined the Erasmus MC Cancer Institute in Rotterdam to continue his work on drug development as head of the phase I unit and shifting the focus of his translational science to urogenital cancer.


Publications

The genomic landscape of metastatic castration-resistant prostate cancers using whole genome sequencing reveals multiple distinct genotypes with potential clinical impact. Lisanne F. van Dessel, Job van Riet, Minke Smits, Yanyun Zhu, Paul Hamberg, Michiel S. van der Heijden, Andries M. Bergman, Inge M. van Oort, Ronald de Wit, Emile E. Voest, Neeltje Steeghs, John W.M. Martens, Stefan Sleijfer, Edwin Cuppen, Wilbert Zwart, Harmen J.G. van de Werken, Niven Mehra, Martijn P. Lolkema bioRxiv 546051; doi: https://doi.org/10.1101/546051

Pan-cancer whole genome analyses of metastatic solid tumors. Peter Priestley, Jonathan Baber, Martijn P. Lolkema, Neeltje Steeghs, Ewart de Bruijn, Charles Shale, Korneel Duyvesteyn, Susan Haidari, Arne van Hoeck, Wendy Onstenk, Paul Roepman, Mircea Voda, Haiko J. Bloemendal, Vivianne C.G. Tjan-Heijnen, Carla M.L. van Herpen, Mariette Labots, Petronella O. Witteveen, Egbert F. Smit, Stefan Sleijfer, Emile E. Voest, Edwin Cuppen bioRxiv 415133; doi: https://doi.org/10.1101/415133

van Dessel LF, Beije N, Helmijr JC, Vitale SR, Kraan J, Look MP, de Wit R, Sleijfer S, Jansen MP, Martens JW, Lolkema MP. Application of circulating tumor DNA in prospective clinical oncology trials - standardization of preanalytical conditions. Mol Oncol. 2017 Feb 6.

Lolkema M, Debets R, de Wit R. Prostate Cancer and Immune Monitoring: Are We Heading Towards Better Selection of Patients and Treatment Strategies. Eur. Urol. 2016 Aug 17

Hoogstraat M, Gadellaa-van Hooijdonk CG, Ubink I, Besselink NJ, Pieterse M, Veldhuis W, van Stralen M, Meijer EF, Willems SM, Hadders MA, Kuilman T, Krijgsman O, Peeper DS, Koudijs MJ, Cuppen E, Voest EE, Lolkema MP. Detailed imaging and genetic analysis reveal a secondary BRAF L505H resistance mutation and extensive intra-patient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib. Pigment Cell Melanoma Res. 2015 May;28(3):318-23.

Lolkema MP, Gadellaa-van Hooijdonk CG, Bredenoord AL, Kapitein P, Roach N, Cuppen E, Knoers NV, Voest EE. Ethical, Legal, and Counseling Challenges Surrounding the Return of Genetic Results in Oncology. 2013 J Clin Onc J Clin Oncol. 2013 May 20;31(15):1842-8.

Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, Lolkema MP, Jiang P, Kultti A, Thompson CB, Maneval DC, Jodrell DI, Frost GI, Shepard HM, Skepper JN, Tuveson DA. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut. 2013 Jan;62(1):112-20

Frese KK, Neesse A, Cook N, Bapiro TE, Lolkema MP, Jodrell DI, Tuveson DA. nab-Paclitaxel Potentiates Gemcitabine Activity by Reducing Cytidine Deaminase Levels in a Mouse Model of Pancreatic Cancer. Cancer Discov. 2012 Mar;2(3):260-9.

Lolkema MP*, Arkenau HT*, Harrington K, Roxburgh P, Morrison R, Roulstone V, Twigger K, Coffey M, Mettinger K, Gill G, Evans TRJ, de Bono JS. A phase-I study of the combination of intravenous reovirus type 3 Dearing and gemcitabine in patients with advanced cancer. Clin. Cancer Res. 2011 Feb 1;17(3):581-8.

Verheul HM*, Lolkema MP*, Qian DZ, Hilkes YH, Liapi E, Akkerman JW, Pili R, Voest EE. Platelets take up the monoclonal antibody bevacizumab. Clin. Cancer Res. 2007 Sep 15;13(18 Pt 1):5341-7

Giles RH, Lolkema MP, Snijckers CM, Belderbos M, van der Groep P, Mans DA, van Beest M, van Noort M, Goldschmeding R, van Diest PJ, Clevers H, Voest EE. Interplay between VHL/HIF1α and Wnt/β-catenin pathways during colorectal tumorigenesis. Oncogene 2006 May 18;25(21):3065-70.

Gallucci S, Lolkema M, Matzinger P. Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 1999 Nov; 5(11): 1249-55.

Other publications: Pubmed


Teaching activities

Course coordinator:

  • Clinical Trial Development Course UMC Utrecht, PhD students and post-graduate researchers, March 12-15, 2013 and March 13-16, 2012
  • Coordinator of Minor Oncology, department of medical oncology Erasmus MC, graduate students medicine, Sep 1- Nov 11, 2015, best evaluated minor of Erasmus MC 2015

Lecturing:

  • Methods in Clinical Cancer Research workshop, FLIMS, post-docteral researchers, June 20-26, 2015-now
  • Training oncology nursing specialists UMC Utrecht, 2012-2015 3 lectures each year on “Diagnostics and pathophysiology”
  • Dutch Society for Oncology (NVVO) “basiscursus oncologie” 2012-2015 2 lectures each year on “General introduction to the concepts of chemotherapy”
  • Certificate of Competence in Breast Cancer 2015-1016
  • Course Basic and Translational Oncology, postgraduate school Molecular Medicine (MolMed) 2016-now
  • Various lectures in post-grad courses

Thesis supervised:

  • Geert Cirkel (UMCU)

Other positions

Medical manager Clinical Trial Center Erasmus MC

Scholarships, grants, and awards

  • 2010 Momenta Pharmaceuticals, M402, a Rationally Designed Heparin Sulfate Mimetic With a Novel Mechanism of Action, Synergizes With Gemcitabine to Improve Survival and Reduce Metastasis in a Murine Model of Pancreatic Cancer
  • 2014 Astellas Pharmaceuticals, Biomarker discovery study to identify a genomic profile predictive for response to enzalutamide in patients with castration resistant prostate cancer
  • 2015 JnJ Pharmaceuticals, Finding the optimal predictors for response to abiraterone
  • 2015 Sanofi Pharmaceuticals, ‘Non-randomized phase 2 open-label multicenter study determining the response to Cabazitaxel in metastatic prostate cancer patients with AR-V7 positive circulating tumor cells (CTCs): CABA-V7’
  • 2016 MSD Pharmaceuticals “RESPONDER study, Biomarker discovery study to identify patients with advanced urothelial cancer benefitting from pembrolizumab treatment

More

Participating in research groups:

  • Center For Personalized Cancer Treatment (CPCT): PI CPCT-02 study
  • OncoDistinct Network: Early Phase trial network Europe (http://www.oncodistinct.net/)

Participating in research projects:

  • Genomic analysis of prostate cancer
  • Biomarker discovery and validation in urogenital cancers
  • Early Phase Clinical Trials

 

My Groups