TRACERx

TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective, multi-region, longitudinal sequencing study that systematically reconstructs tumor phylogenies across space and time. Two main arms exist:

• TRACERx Lung: Focuses on non-small cell lung cancer (NSCLC). Demonstrated that chromosomal-instability confers increased risk of recurrence and death independently of known predictive markers (Jamal-Hanjani et al., 2017).
• TRACERx Renal: Focuses on clear cell renal cell carcinoma (ccRCC). Revealed that distinct evolutionary trajectories (punctuated-evolution vs. gradual Darwinian) determine clinical phenotype and metastatic patterns (Turajlic et al., 2018a, 2018b).

TRACERx is the primary source of prospective clinical evidence linking clonal evolutionary dynamics to patient outcomes.

Al Bakir et al. (2023) reported the TRACERx 421 cohort’s metastasis evolution analysis: 126 NSCLC patients with paired primary-metastasis WES. Key findings: ~75% of metastases diverge late (after the last clonal sweep); polyclonal dissemination in 32% is associated with extrathoracic recurrence; primary LN metastases rarely seed further disease (<20%); metastasis-seeding clones exhibit positive selection in the primary tumour (dN/dS > 1 in lung cancer genes); single-region primary sampling misclassifies 83% of late divergence as early.