Mutations and associated gene expression alterations that disrupt normal tissue homeostasis in cancerous cells accumulate progressively also during cancer therapy. The resulting continuous increase of genetic heterogeneity and genome instability over time and space provide a rich substrate for Darwinian selection of subpopulations of cancer cells called subclones that are therapy-resistant and thus continue to grow at the expense of others.

Monitoring of such intratumoral heterogeneity longitudinally in real time and at the molecular level is important both for accurate prognosis and to guide the choice of existing anticancer drugs and future precision medicines against the emergence of drug resistance. However, methods to detect subclones with new driver mutations and dynamic changes in their spatiotemporal distribution and in infiltrating immune cells and other components of the tumor microenvironment in solid cancers are still in their infancy.

Therefore, the goal of this focus area is to foster the development of new technologies to detect and quantify intratumoral heterogeneity and its dynamics in real time and with high sensitivity, and to decipher how cancer cells and their microenvironment co-evolve in order to identify new vulnerabilities of these complex ecosystems and exploit them therapeutically using combinations of existing and new precision medicines.