Chemotherapy Reactivates Dormant Cancer Cells — Triggers Metastasis
New landmark study reveals that standard cancer treatment can backfire — with devastating consequences.
Chemotherapy is supposed to kill cancer — not bring it back. But a groundbreaking Cancer Cell study by He et al has revealed that common cancer drugs like doxorubicin and cisplatin can reawaken dormant tumor cells, triggering deadly metastatic relapses — especially in the lungs.
These “sleeping” cancer cells, known as disseminated tumor cells (DTCs), can lie hidden for years before reactivating. This study is the first to directly prove that chemotherapy itself can wake them up.
Chemotherapy Reactivates Dormant Cancer Cells
Using DormTracer, the team showed that chemo-treated mice had a surge of previously dormant cancer cells re-entering the cell cycle.
These reawakened cells formed aggressive lung metastases weeks after chemo — even in cases where the primary tumor was gone.
This effect was specific to dormant cells; chemo suppressed active tumors but inadvertently activated the sleeping ones.
Neutrophil Extracellular Traps (NETs) Are the Trigger
Chemotherapy didn't just hit cancer cells — it also caused fibroblasts in the lung to enter a state called senescence (biological aging).
These senescent cells released pro-inflammatory signals that activated neutrophils — a type of white blood cell.
The neutrophils formed NETs — sticky webs of DNA and enzymes like MMP9 and neutrophil elastase — which remodeled the lung microenvironment and directly triggered dormant DTCs to awaken.
SASP Proteins (C3, MIF, CXCL1) Drive This Chain Reaction
The senescent fibroblasts released a toxic cocktail known as SASP (senescence-associated secretory phenotype).
Three key factors — Complement C3, Macrophage Migration Inhibitory Factor (MIF), and CXCL1 — were identified as major drivers of NET formation.
Mice engineered to lack C3 had far less NET activity and lower rates of metastasis after chemo.
Blocking NETs or Clearing Senescent Cells Prevents Relapse
Administering DNase I (which breaks up NETs) or GSK484 (a PAD4 inhibitor that blocks NET formation) completely prevented chemo-triggered metastasis in mice.
Giving Dasatinib + Quercetin (a senolytic combo) cleared out the senescent fibroblasts and shut down the entire cascade — resulting in both primary tumor control and no relapse.
Importantly, this combination didn’t reduce chemo’s effectiveness at shrinking the primary tumor.
The Mechanism Was Confirmed in Humans
In breast cancer patients, lung metastases had higher NET density and elevated C3, MIF, and CXCL1 levels after chemotherapy.
Blood samples showed C3 and MIF spiked after treatment — especially in patients who later developed lung relapse.
These markers could become predictive biomarkers for relapse risk in future screening.
https://www.thefocalpoints.com/p/breaking-chemotherapy-reactivates