Publications by authors named "L Kiedrowski"
Unlabelled: While tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC), clinical outcomes vary and acquired resistance remains a significant challenge. We conducted a retrospective study of patients with ALK-positive NSCLC who had clinico-genomic data independently collected from two academic institutions (n = 309). This was paired with a large-scale genomic cohort of patients with ALK-positive NSCLC who underwent liquid biopsies (n = 1,118).
View Article and Find Full Text PDFArticle Synopsis
- MET amplification serves as a common resistance mechanism for patients with ALK-rearranged lung cancer, showing varied responses to treatment combinations targeting both ALK and MET.
- A study analyzed over 50 lung cancer specimens and found that 75% exhibited high-level MET amplification, indicating significant intralesional variability, though such high-level amplification was rare in plasma samples.
- Additionally, MET-amplified tumors often carried TP53 mutations and had notable differences in genetic alterations compared to non-MET-amplified ALK-rearranged cases.
Purpose: Immune checkpoint inhibitors are approved for advanced solid tumors with microsatellite instability-high (MSI-H). Although several technologies can assess MSI-H status, detection and outcomes with circulating tumor DNA (ctDNA)-detected MSI-H are lacking. As such, we examined pan-cancer MSI-H prevalence across 21 cancers and outcomes after ctDNA-detected MSI-H.
View Article and Find Full Text PDFArticle Synopsis
- Amplification acts as a resistance mechanism in ALK+ lung cancer, and this study focuses on treatment outcomes for patients with this specific molecular profile.
- A cohort of 12 patients receiving combined ALK and MET-targeting regimens showed partial responses in 42% of cases, highlighting some effectiveness but also significant side effects, such as peripheral edema.
- The findings suggest that while there is moderate antitumor activity from combined therapy, further prospective studies are needed to better understand benefits and target suitable patients.
Purpose: PARP inhibitors (PARPi) provide an effective maintenance option for patients with BRCA- or PALB2-mutated pancreatic cancer. However, mechanisms of PARPi resistance and optimal post-PARPi therapeutic strategies are poorly characterized.
Experimental Design: We collected paired cell-free DNA samples and post-PARPi clinical data on 42 patients with advanced, platinum-sensitive pancreatic cancer who were treated with maintenance rucaparib on NCT03140670, of whom 32 developed progressive disease.