Oncology

FMT as an adjunct strategy to enhance ICI efficacy in solid tumors

Recent randomized trials indicate that fecal microbiota transplantation can enhance first-line ICI efficacy in RCC, melanoma, and NSCLC. Clinical benefit is linked to functional gut microbiome remodeling, including depletion of taxa associated with ICI resistance. Systemic immunometabolic shifts after FMT suggest improved T-cell function and intratumoral immune activation. These data support continued development of standardized microbiome-directed interventions to augment checkpoint blockade in solid tumors. 1

Chemo–IO ± VEGF inhibition after EGFR-TKI failure in EGFR-mutant NSCLC

Across seven RCTs including 2196 patients, adding ICIs to chemotherapy modestly extended PFS versus chemotherapy alone after EGFR-TKI failure. Chemo–IO with VEGF inhibition achieved median PFS 8.1 versus 5.5 months (HR 0.59), and without VEGF inhibition 5.6 versus 5.5 months (HR 0.83). Median OS improved with chemo–IO plus VEGF inhibition (19.0 vs 15.7 months; HR 0.77) and with chemo–IO alone (18.1 vs 15.7 months; HR 0.86). Adding VEGF blockade to chemo–IO did not significantly extend OS versus chemo–IO alone, despite PFS and response gains. Patients with PD-L1 ≥1% or L858R mutations derived greater PFS benefit, underscoring the need for biomarker-driven selection. 2

STAT3-driven stemness and telomerase in EGFR-TKI–resistant NSCLC

In NSCLC models, EGFR-TKI–mediated MAPK inhibition rapidly activated STAT3, promoting resistance. RNA-seq and functional assays showed STAT3 upregulated stemness markers and telomerase, supporting a drug-tolerant, stem-like phenotype. Pharmacologic STAT3 blockade, including with icaritin, enhanced EGFR-TKI antitumor activity in cell and mouse models. These findings nominate STAT3 and telomerase programs as rational combination targets to delay or overcome EGFR-TKI resistance. 3