Where academic tradition
meets the exciting future

You are here: TUCS > PUBLICATIONS > Publication Search > Individualized Systems Medicin...

Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia

Tea Pemovska, Mika Kontro, Bhagwan Yadav, Henrik Edgren, Samuli Eldfors, Agnieszka Szwajda, Henrikki Almusa, Maxim M. Bespalov, Pekka Ellonen, Erkki Elonen, Bjørn T. Gjertsen, Riikka Karjalainen, Evgeny Kulesskiy, Sonja Lagström, Anna Lehto, Maija Lepistö, Tuija Lundán, Muntasir Mamun Majumder, Jesus M. Lopez Marti, Pirkko Mattila, Astrid Murumägi, Satu Mustjoki, Aino Palva, Alun Parsons, Tero Pirttinen, Maria E. Rämet, Minna Suvela, Laura Turunen, Imre Västrik, Maija Wolf, Jonathan Knowles, Tero Aittokallio, Caroline A. Heckman, Kimmo Porkka, Olli Kallioniemi, Krister Wennerberg, Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia. Cancer Discovery 3(12), 1416–1429, 2013.

Abstract:

We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response subtypes based on DSRT profiles, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3-ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution and novel genomic changes potentially explaining resistance, whereas ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs.
SIGNIFICANCE:
Here, we demonstrate an ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy. This approach could facilitate systematic drug repositioning of approved targeted drugs as well as help to prioritize and de-risk emerging drugs for clinical testing.

BibTeX entry:

@ARTICLE{jPeKoYaEdElSzAlBeElElGjKaKuLaLeLeLuMaLoMaMuMuPaPaP,
  title = {Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia},
  author = {Pemovska, Tea and Kontro, Mika and Yadav, Bhagwan and Edgren, Henrik and Eldfors, Samuli and Szwajda, Agnieszka and Almusa, Henrikki and Bespalov, Maxim M. and Ellonen, Pekka and Elonen, Erkki and Gjertsen, Bjørn T. and Karjalainen, Riikka and Kulesskiy, Evgeny and Lagström, Sonja and Lehto, Anna and Lepistö, Maija and Lundán, Tuija and Majumder, Muntasir Mamun and Lopez Marti, Jesus M. and Mattila, Pirkko and Murumägi, Astrid and Mustjoki, Satu and Palva, Aino and Parsons, Alun and Pirttinen, Tero and Rämet, Maria E. and Suvela, Minna and Turunen, Laura and Västrik, Imre and Wolf, Maija and Knowles, Jonathan and Aittokallio, Tero and Heckman, Caroline A. and Porkka, Kimmo and Kallioniemi, Olli and Wennerberg, Krister},
  journal = {Cancer Discovery},
  volume = {3},
  number = {12},
  pages = {1416–1429},
  year = {2013},
}

Belongs to TUCS Research Unit(s): Biomathematics Research Unit (BIOMATH)

Publication Forum rating of this publication: level 1

Edit publication