Oncotarget

Research Papers:

Multi-omic based molecular profiling of advanced cancer identifies treatable targets and improves survival in individual patients

Alexandra Samsen _, Silvia von der Heyde, Carsten Bokemeyer, Kerstin A. David, Bernd Flath, Max Graap, Bianca Grebenstein, Ludger Heflik, Wiebke Hollburg, Peter Layer, Eike von Leitner, Friedrich Overkamp, Wolfgang Saeger, Sandra Schneider, Cay-Uwe von Seydewitz, Axel Stang, Alexander Stein, Carsten Zornig and Hartmut Juhl

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Oncotarget. 2018; 9:34794-34809. https://doi.org/10.18632/oncotarget.26198

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Abstract

Alexandra Samsen1, Silvia von der Heyde2, Carsten Bokemeyer3, Kerstin A. David2, Bernd Flath4, Max Graap1, Bianca Grebenstein1, Ludger Heflik5, Wiebke Hollburg4, Peter Layer6, Eike von Leitner1, Friedrich Overkamp7, Wolfgang Saeger1, Sandra Schneider1, Cay-Uwe von Seydewitz8, Axel Stang9, Alexander Stein3, Carsten Zornig6 and Hartmut Juhl1

1IndivuTest GmbH, Hamburg, Germany

2Indivumed GmbH, Hamburg, Germany

3II. Medical Clinic and Polyclinic, Department of Oncology, Hematology, Bone Marrow Transplantation and Pneumology, University Cancer Center Hamburg, Hubertus Wald Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

4HOPA-Hämatologisch−Onkologische Praxis Altona, Hamburg, Germany

5Praxis Und Tagesklinik Für Internistische Onkologie und Hämatologie, Recklinghausen, Germany

6Israelitisches Krankenhaus, Hamburg, Germany

7Oncologianova GmbH, Recklinghausen, Germany

8Medizinische Klinik, Onkologie/Hämatologie Und Palliativmedizin, Krankenhaus Reinbek St Adolf-Stift, Reinbek, Germany

9Department of Hematology, Oncology and Palliative Medicine, Asklepios Klinik Barmbek, Hamburg, Germany

Correspondence to:

Alexandra Samsen, email: samsen@indivutest.com

Keywords: molecular profiling; advanced stage IV cancer; MAPK pathway; PI3K/AKT/mTOR pathway; targeted therapy

Received: August 03, 2018     Accepted: September 10, 2018     Published: October 05, 2018

ABSTRACT

A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-generation sequencing and phosphoprotein profiling. Expression and phosphorylation of key oncogenic pathways were measured to identify targets at the (phospho-) proteomic level. At genomic level, 50 oncogenes and tumor suppressor genes were analyzed. Based on molecular profiling, targeted therapies were decided by the attending oncologist. Accordingly, 28 patients who met the defined criteria fell in two equal-sized groups. One group received targeted therapies while the other did not. Following six months of treatment, disease control was achieved by 49% of patients receiving targeted therapy (complete remission, 14%; partial remission, 21%; stable disease, 14%; disease progression, 36%; death, 14%) and 21% of patients receiving non-targeted therapy (stable disease, 21%; disease progression, 64%; death, 14%). Individual patients experienced dramatic responses to a therapy which otherwise would not have been applied. This approach clarifies the value of multi-omic molecular profiling for cancer diagnostics.


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