Olli Kallioniemi's group
Precision Cancer Medicine
Making cancer care more effective and individualized is a central aim for cancer researchers worldwide. This is usually being pursued via DNA sequencing based efforts by the identification of oncogenic driver mutations. We believe and have emerging evidence that this will miss many therapeutic opportunities and additional endpoints including cell-based functional testing should be examined. Toward these goals, we carry out comprehensive ex vivo drug efficacy testing on patient-derived cells along with –omics profiling. We believe this approach will help to personalize treatment, aid in prioritizing drugs for clinical testing, provide for intelligent selection of drug combinations and improve treatment outcomes. Our work has a strong translational angle and is often carried out while the patient is receiving care. Our goal is to provide the treating clinician with additional treatment options should there be a need.
Initially we explored this functional drug testing platform in acute myeloid leukemia (AML) where the relevant material is more readily available. We have now also advanced to solid tumors including but not limited to ovarian, prostate and renal cancer. In solid tumors, relevant patient-derived ex vivo models are less readily available and the limited amount of tissue can be a challenge. Towards this we use different reprogramming methods of patient-derived primary cells in 2D, as well as 3D organoid cultures. We carry out genomics profiling of both tissue and model to ensure representativity of the cell models.
We have mapped the translational progress of our work into three phases, where phase I represents testing feasibility of model development. In phase II model development is doable, but representativity is still not optimal and no translation into treatment has been achieved. Phase III constitutes the final stage, where the cell models have generated actionable drugs that have been used in patient treatment. Our work is carried out in parallel both at the Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet in Stockholm, Sweden and at the Institute for Molecular Medicine Finland in Helsinki, Finland.
Science for Life Laboratory (SciLifeLab)
171 21 Solna
Science for Life Laboratory (SciLifeLab)
171 65 Solna
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Olli Kallioniemi, professor, director at the Science for Life Laboratory (SciLifeLab)
Hanna Axelsson, project manager
Tom Erkers, assistant professor
Emilie Flaberg, postdoc
Greta Gudoityte, lab engineer
Tojo James, bioinformatician
Kasper Karlsson, assistant professor
Francesco Marabita, bioinformatician
Elisabeth Moussaud, lab manager
Madiha Nazir, postdoc
Se Whee Sammy Park, lab engineer
Brinton Seashore Ludlow, assistant professor
Osheen Sharma, lab engineer
Nona Struyf, lab engineer
Susanne Wikblad, personal assistant
Emma Åkerlund, postdoc
Päivi Östling, associate professor, co-PI
Consistency in drug response profiling.
Mpindi J, Yadav B, Östling P, Gautam P, Malani D, Murumägi A, et al
Nature 2016 11;540(7631):E5-E6
Comprehensive Drug Testing of Patient-derived Conditionally Reprogrammed Cells from Castration-resistant Prostate Cancer.
Saeed K, Rahkama V, Eldfors S, Bychkov D, Mpindi J, Yadav B, et al
Eur. Urol. 2017 03;71(3):319-327
Impact of normalization methods on high-throughput screening data with high hit rates and drug testing with dose-response data.
Mpindi J, Swapnil P, Dmitrii B, Jani S, Saeed K, Wennerberg K, et al
Bioinformatics 2015 Dec;31(23):3815-21
Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation.
Pemovska T, Johnson E, Kontro M, Repasky G, Chen J, Wells P, et al
Nature 2015 Mar;519(7541):102-5
Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia.
Pemovska T, Kontro M, Yadav B, Edgren H, Eldfors S, Szwajda A, et al
Cancer Discov 2013 Dec;3(12):1416-29
Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML.
Malani D, Murumägi A, Yadav B, Kontro M, Eldfors S, Kumar A, et al
Leukemia 2017 05;31(5):1187-1195
Monitoring therapy responses at the leukemic subclone level by ultra-deep amplicon resequencing in acute myeloid leukemia.
Ojamies P, Kontro M, Edgren H, Ellonen P, Lagström S, Almusa H, et al
Leukemia 2017 05;31(5):1048-1058