The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

ABSTRACT:

Background

Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Patients and methods

DRUP is a prospective, pan-cancer, non-randomized clinical trial (NCT02925234) that treats patients with therapy-refractory metastatic cancer and an actionable molecular profile using matched off-label targeted and immunotherapies. All patients treated with TT with available clinical outcomes and whole genome sequencing were included. PAL was determined based on driver gene alterations and correlated with

SUBMITTER: Verkerk K 

PROVIDER: S-EPMC11760820 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature