Drug-tolerant persister cells in cancer

The EML4-ALK oncogene forms  cytoplasmic protein condensates that are associated with its oncogenic signaling. Here, the authors demonstrate that these EML4-ALK assemblies also sequester receptor tyrosine kinase (RTK) adapter proteins suppressing signaling which was reversed upon ALK inhibition, resulting in rapid resensitisation to growth factors and tumor cell survival.

An integration of 3D chromatin structure and gene expression at single-cell resolution has not yet been demonstrated. Here, authors develop a multi-omic data integration algorithm applied to a breast cancer model, identifying topologically conserved domains and integrated subpopulations.

Here, using single-cell omics and genomic barcoding, the authors identify transcriptional states and DNA accessibility profiles linked to tumour initiation and drug tolerance, highlighting the complexity of cancer. This study suggests that cancer evolution is driven by pre-encoded factors.

Emergence of drug tolerant cells drives adaptive targeted therapy resistance in non-small cell lung cancer (NSCLC). Here, the authors identify a common molecular event underpinning resistance to multiple targeted therapies in a panel of mutant NSCLC models that can be targeted with farnesyltransferase inhibition.

The mechanisms leading to acquired resistance to targeted therapy in cancer are not completely understood. Here, the authors show that ferritinophagy mediates adaptive resistance to Osimertinib, and that combining this EGFR tyrosine kinase inhibitor with copper ionophores improves its therapeutic efficacy in preclinical models of non-small cell lung cancer.

Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.