Generation and validation of a panel of EMT reporter cell lines from solid tumors

Cancer is a very heterogeneous disease and its subtypes display great variability in their response to treatment.

The high failure rate of anticancer drug discovery consumes billions of dollars annually, contributing to the high cost of those few drugs that are eventually approved. One of the problems lies in inaccurate and oversimplified cell line models for studying human tumors. Yet, a method to incorporate tumour subtype contribution in response to drugs is lacking.

To improve experimental oncology and drug discovery, we propose to develop a validated toolkit of ready-to-use cell lines and defined cell culture media in order to clearly and unambiguously represent well conserved solid tumor subtypes.

This approach is drawn from our ERC StG-funded project, in which we invented, validated and patented a method to genetically label any cell type or cell state transition.

Our idea is novel because it uses custom synthetic genetic reporters in in vitro tumor models, which enables tracing of tumor cell states.

The first component of the kit is a set of genetically modified cell lines representing tumors from different epithelial tissues and reporting on epithelial or mesenchymal states (work package1; WP1).

Thereafter, we will use these cells to define the formulation of two additional components of the kit: i) the cell culture media and ii) the supplements to in vitro propagate and discriminate the two distinct cell states (WP2-WP3).

In WP4, we will perform a product comparison, by measuring the features of the toolkit cell lines in response to anti-cancer treatment as compared to current standards. In parallel, WP5-WP6 will address industry-quality, IP strategy implementation and freedom-to-operate.

Given the socioeconomic impact of cancer and the lack of a similar technology, our solution has the potential to eliminate the high failure rate of anticancer drug discovery because it will make it possible to perform drug screens on different tumor cell states at once.