Combating cancer via a data-driven hallmark strategy: From discovery to precision therapies in Acute Myeloid Leukemia (AML)

The cancer hallmark concept was coined 20-years ago and has served as a powerful foundation for cancer research.

We have developed a novel data-driven way to construct cancer hallmarks and suggest here to promote precision medicine based on this concept.

Our multi-omic profiling of 160 Swedish patients with acute myeloid leukemia (AML), along with drug testing of 500+ cancer drugs, led to the definition of 11 AML hallmarks.

As compared to the original theoretical cancer hallmark concept, these represent actual, quantifiable molecules and pathways with associated drug responses (e.g. cytokine signaling, differentiation, epigenetic signaling, cell growth, stem cell signals, metabolism, splicing and transcriptional regulation).

In this study, we have designed the following aims to bring the data-driven cancer hallmark strategy towards translational implementation in AML: 1) Develop specific diagnostic assays for the AML hallmarks, 2) Evaluate the predictivity of hallmarks-based therapy allocation and 3) Define therapeutic combinations for AML and study hallmark plasticity.

We believe the data-driven cancer hallmark strategy is powerful for uncovering exciting biological, functional and drug associations, and could be applied for diagnostic profiling and therapeutic tailoring in AML.

These studies in AML will provide an example on how systems biological studies in other cancer types could rapidly be translated to clinical implementation, including tailor-made drug combinations.