SNIC SUPR
Precision Cancer Medicine /singel cell seq
Dnr:

sens2018619

Type:

SNIC SENS

Principal Investigator:

Päivi Östling

Affiliation:

Karolinska Institutet

Start Date:

2019-01-09

End Date:

2021-02-01

Primary Classification:

30402: Biomedical Laboratory Science/Technology

Allocation

Abstract

Cancer treatment is impeded by cancer heterogeneity, development of resistance to therapy and the slow speed of introduction for new therapies and their associated costs. In practice, large groups of patients receive fixed cancer treatment schemes despite complex individual variability and disease evolution. The question arises; Can we improve outcome by optimizing existing therapies available on an individual level? Our hypothesis is that these challenges can be overcome by functional testing ex vivo to identify the most effective drug for an individual patient at the right time. Our laboratory is currently applying high-throughput drug sensitivity and resistance testing of patient cells ex vivo. In this paradigm, cancer cells from the patient are tested against 525 conventional and investigative oncology drugs in a 5-point concentration range to determine optimal treatment options. In the current proof-of-concept project, we will use single-cell RNA sequencing to ex vivo track transcriptional cancer heterogeneity evolution over time after treatment with today’s standard induction therapy in patients with acute myeloid leukemia. We will also label and multiplex cancer cells from the different conditions after our drug screen assay and perform single-cell RNA sequencing. Using these results, we anticipate that we can identify a set of drugs that together would be effective to eliminate the entire spectrum of the cancer heterogeneity and thus create combinatorial or sequential treatment options for each patient. The goal is to later leverage this platform to provide therapeutic options for individual patients and generate information to impact clinical decision-making for the treatment of patients with acute myeloid leukemia. The study is approved by the regional ethical review board (Dnr: 2017/2085-31/2) and will be performed in line with the ethical guidelines of the Swedish Research Council.