The lab: Wennerberg group

Lab's research themes:

Our work is focused on acute myeloid leukemia and high-grade serous ovarian cancer goal is to understand mechanisms of drug sensitivity and resistance in individual cancers and in particular the subsets of cells that persist current therapies and drive cancer recurrence. Through this knowledge, we aim to identify new effective cancer precision medicine strategies that can be explored in clinical trials. Our overarching research questions are:

• Can we identify and understand the drug resistant cells in a cancer, including the cells that have the capacity to regrow new tumors?
• Can we identify “druggable” vulnerabilities in these cells?
• From the molecular and phenotypic profiles of an individual cancer, can we predict drug resistance mechanisms and the therapeutic approaches that overcome them?
• Can these discoveries be translated to clinical efficacy?

Merits of the lab:

Our group study primary cancer samples by combining ex vivo drug sensitivity testing and genetic screening with molecular profiling. Our work has shown that cancer precision medicine greatly benefits from being guided by more than genomics alone, and that ex vivo drug sensitivity testing has a great translational potential. Our research efforts in this scientific area over the last decade have led to novel understanding of the biology of cancers, discoveries that can and have been translated to the clinic, and in significant tools and resources that benefit the scientific community.

Why do we want medical doctors?

Our team is a group of 14 members from 11 countries with diverse training backgrounds. We currently do not have any medical doctors on the team but we collaborate closely with both junior and senior clinicians and clinical researchers in all our projects.

Country: Denmark
Supervisor: Krister Wennerberg

The position

What’s the main purpose of our research?

The pro-apoptotic BCL-2 inhibitor venetoclax is changing the treatment of elderly and unfit patients suffering from acute myeloid leukemia (AML). When combined with azacitidine, a standard-of-care hypomethylating agent, venetoclax induces remissions in the majority of elderly/unfit AML patients and overall survival is significantly extended. However, most, if not all, cases will eventually relapse and there are currently no viable and effective approaches to treat venetoclax-azacitidine-relapsed patients. We, therefore, need to understand and be able to predict the mechanisms of resistance for this therapy better and identify clinically relevant ways to avoid or overcome resistance development.

How we will do it?

You will be using a unique set of samples from two clinical trials where AML patients have been treated with venetoclax-azacitidine. We have patient samples both from responding and non-responding cases as well as paired sets of samples at diagnosis (treatment-sensitive) and at relapse (treatment-resistant) and are all clinically annotated and molecularly profiled. Using state-of-the-art experimental methodologies, you will explore these patient samples to gain a new profound understanding of the molecular, phenotypic and genetic mechanisms behind resistance to the venetoclax-azacitidine in AML and most importantly, how resistance could be overcome or prevented. Working with clinical hematologists across the Nordic countries, the goal is that your discoveries will be converted into clinical trials where we explore new therapies for overcoming venetoclax-azacitidine resistance in AML patients.

Why is this important?

As the venetoclax-azacitidine treatment is becoming the standard therapy for elderly and unfit AML patients, the next clinical frontier will be how to tackle the treatment resistance that will emerge in most cases. You will be addressing this challenge in collaboration with a multidisciplinary team of experimental and clinical scientists.

Who is a good fit for the project?

The project is based on generating new experimental evidence for translational discoveries. As such, you will benefit from having a passion both for performing wet-lab experiments and the analysis of complex sets of experimental and clinical data to make fundamental discoveries that have the potential to be turned into new therapies. A background in, or profound interest in, hematology is highly valued.

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