The Knott lab combines computational biology and functional genomics to elucidate the factors that govern cancer progression.
In August 2016, the Knott lab was formed at Cedars-Sinai Medical Center in Los Angeles, California. Here, we aim to develop therapies that target the intercellular relationships within tumors that promote progression and resistance to current and experimental therapies.
Drug discovery: Past, Present and Future
The “war on cancer” was founded upon the premise that an understanding of tumor biology would lead to effective cancer treatments. This philosophy is embodied by profiling studies that search the molecular signatures of tumors for indicators of effective treatment options. Initially, these studies were predicated on the notion that the discovery of so-called “driver mutations” would afford therapeutic opportunities. Although the strategy of targeting these alterations has produced stunning responses, these effects are invariably short-lived, as the plasticity of cancer cells allows them to evade these targeted therapies. Underlying this resistance is the ability of cancer cells to manipulate other tumor cells types into providing an environment that is protective against therapeutic onslaught. It is now argued that curative responses will only be achieved by understanding and targeting these cellular interactions.
The goal of the Knott Lab is to develop cancer treatment strategies that are focused on the interactions between malignant and non-malignant tumor cells, which drive disease progression. This work entails developing and interrogating models of resistance to established and experimental therapies. In addition, the lab applies novel profiling methods to study patient tumors so that the cellular interactions driving the diseased tissue can be ascertained. By applying the knowledge that is gained from studying clinical material to focus questions asked of the model systems, the lab hopes to identify rationally guided therapeutic strategies to halt disease progression.