🔍 Stress‑adaptive, slow‑cycling “persister” programs—marked by DUSP1 and KLF4—emerge in ER+/HER2− models, revealing new insights into chemotherapy tolerance.
🔬 Tracking resistance at single‑clone resolution changes how we think about treatment failure.
lvnguyenlab.ca/2026/04/06/p...
🧬 Using single‑cell barcoding and scRNA‑seq across breast cancer xenografts, we show that chemotherapy rapidly rewires the tumor cellular clonal landscape. Treatment selects for previously rare, resistant cell clones, with distinct responses across cell states and subtypes.
🚨 Pre-print alert! Kronheim S et al. Chemotherapy reshapes cellular clonal landscape via persister programs in breast cancer xenografts: doi.org/10.64898/202...
In collaboration with @carloscaldas1960.bsky.social & @fgaiti.bsky.social
#CancerResearch #SingleCell #Chemotherapy #TumorEvolution
Important protocol from @nguyenlab.bsky.social that details method used in our paper published recently @cp-cellreports.bsky.social: www.cell.com/cell-reports...
www.sciencedirect.com/science/arti...
Online now: The tumor microenvironment of 14,837 breast cancers is associated with clinical outcome independently of genomic subtypes
My poor laptop wishes I learned how to use the cluster earlier, but it’s sacrifice was not in vain! We learned some important things about the breast cancer tumor microenvironment, described in our paper published today:
www.cell.com/cell-reports...
Here's the 🧵
Most #cancer cells aren’t able to propagate tumours—but a rare few can.
Using genetic barcodes, a team @pmresearch-uhn.bsky.social tracked these rare clones—revealing how they evolve, adapt, and resist treatment. A step toward more targeted cancer therapies.
🔗: www.uhnresearch.ca/news/rare-ca...
Altogether, we illustrate the dynamic nature of transcriptional plasticity in propagating clones, highlighting their ability to evolve, adapt, and mature into dominant clones that constitute the majority of tumor cells in secondary xenografts, all originating from a single barcoded cell.
Dominant propagating clones display dynamic transcriptional plasticity which we illustrate by profiling gene expression across generations of cells derived from single starting cells.
Dichotomous cell populations in basal breast cancer distinguish between functional clone types based on differential signaling and metabolic responses. This suggests it is possible to enrich for cells with propagating activity.
In vivo clone doubling time, a metric used to quantify the rate of clonal growth, reveals breast cancer subtype-specific differences in clonal fitness.
We show that extremely rare cells can give rise to clones with propagating activity (frequency 1 in 15,000 – 1 in 116,000). Dominant propagating clones regenerate the full model-specific transcriptional landscape and there is a conserved differentiation program.
In this paper we used expressed lentiviral barcoding to track the clonal growth of over 20,000 single-cell-derived clones in 110 xenografts from 26 patient-derived breast cancer xenograft models. We also profiled 167,375 single-cell RNA profiles to link clonal growth with gene expression.
I am excited to share the latest publication from the Nguyen, Caldas @carloscaldas1960.bsky.social and Rueda labs @ruedalab.bsky.social. This was a massive effort from a fantastic team and I’m grateful to everyone on the paper for their work on this project! doi.org/10.1016/j.ce...
#bcsm #PDTX
