Melanoma: New Combination Therapy Targets Resistant Tumors

MedicalResearch.com Interview with:

Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands

Dr. Peeper

Daniel S. Peeper, PhD
Professor of Functional Oncogenomics (VUmc)
Member of Oncode Institute
Head, Division of Molecular Oncology & Immunology
Chair, Scientific Faculty Council
Chair, Translational Research Board
The Netherlands Cancer Institute
Amsterdam The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting.

Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study. 

MedicalResearch.com: What should readers take away from your report?

Response: Although it is generally realized that tumors, whether prior to treatment or upon acquisition of treatment resistance, commonly show heterogeneity, and that this can be associated with distinct therapy responses, such information is not yet used for the more precise and effective clinical management of cancer.

We for the first time, developed a new combination strategy that specifically targets tumor heterogeneity, in this case of melanoma. By characterizing the distinct populations we observed commonly in drug-resistant melanoma, we designed a new combination strategy specifically aiming to target their different therapy sensitivities. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: That tumor heterogeneity is taken into account: that these results can guide rational combination treatments for other cancer types, too.”

Disclosures: This research was funded by Genmab, KWF (Dutch Cancer Society) and the European Research Council.

Citations:

Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors

Julia Boshuizen Louise A Koopman, Oscar Krijgsman, Aida Shahrabi,
Elke Gresnigt– van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd
, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank
, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper & Paul W H I Parren
Nature Medicine
doi:10.1038/nm.4472
Received: 28 March 2017 Accepted: 15 December 2017

https://www.nature.com/articles/nm.4472

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