Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

Bo Mi Ku



Author of

  • +

    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      P2.01-064 - Co-Existing Mutations and Their Clinical Implications in Non-Small Cell Lung Cancer: Korean Lung Cancer Consortium (KLCC-13-01)   (ID 8838)

      09:00 - 16:00  |  Presenting Author(s): Bo Mi Ku

      • Abstract

      Background:
      Non-small cell lung cancer (NSCLC) is a common type of cancer with typically poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to characterize the mutational landscape of NSCLC and identify biomarkers to predict patient outcome.

      Method:
      Archived DNA was extracted from formalin-fixed, paraffin-embedded, mostly small biopsy samples of 162 patients. Targeted sequencing of genomic alterations was conducted using Ion AmpliSeq Cancer Hotspot Panel v2.

      Result:
      The median age of patients was 64 years (range; 32-83 years) and the majority had stage IV NSCLC at the time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had novel or hotspot mutations (range: 1-16 mutated genes). Hotspot mutations were found in 20 genes. Three of the most frequently found hotspot mutations were in TP53 (82, 51.2%), EGFR (66, 40.8%), and STK11 (19, 11.7%). Given that 72.7% (48/66) of EGFR mutant patients were treated with EGFR TKIs, there was a significant difference in overall survival between EGFR mutant and EGFR wild-type patients. In EGFR wild-type subgroup analysis, TP53 status was associated with poor overall survival, while STK11 status was associated both poor progression-free survival and overall survival.

      Conclusion:
      These results suggest that targeted next-generation sequencing using small biopsy samples is feasible and allows for the detection of both common and rare mutations that have independent prognostic value.

  • +

    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
    • +

      P3.03-012 - The Relationship between Efficacy of Wee1 Inhibitor AZD1775 and Mutational Status of TP53 in KRAS-Mutant Non-Small Cell Lung Cancer (ID 8844)

      09:30 - 16:00  |  Presenting Author(s): Bo Mi Ku

      • Abstract

      Background:
      KRAS is frequently mutated in non-small cell lung cancer (NSCLC). However, direct targeting of KRAS has proven to be challenging, and inhibition of KRAS effectors has resulted in limited clinical efficacy. Wee1 kinase is an important regulator of the G2 checkpoint and is overexpressed in various cancers. Inhibition of Wee1 exerts anticancer effects as a monotherapy or in combination with DNA-damaging agents when cancer cells harbor TP53 mutations. However, its role in KRAS-mutant NSCLC, especially as a single agent, has not been explored.

      Method:
      Here, we investigate the anticancer potential of Wee1 inhibitor AZD1775 as a monotherapy and uncover a possible cellular context underlying sensitivity to AZD1775. Eight KRAS-mutant NSCLC cell lines were treated with AZD1775 and cell viability, proliferation, and cell cycle were analyzed. Target modulation was assessed by Western blotting and immunohistochemistry.

      Result:
      Our data show that treatment with AZD1775 significantly inhibited cell survival, growth, and proliferation of TP53-mutant (TP53[MUT]) compared to TP53 wild-type (TP53[WT]) in KRAS-mutant (KRAS[MUT]) NSCLC cells. In KRAS[MUT]/TP53[MUT] cells, AZD1775 treatment led to DNA damage, a decrease of survival signaling, and cell death by apoptosis. Interestingly, cell death through apoptosis was found to be heavily dependent on specific cellular genetic context, rather than inhibition of Wee1 kinase activity alone. In addition, AZD1775 treatment was well tolerated and displayed single-agent efficacy in a mouse xenograft model.

      Conclusion:
      This study provides rationale for inhibiting Wee1 using AZD1775 as a potential anticancer therapy against the TP53[MUT] subgroup of KRAS[MUT] NSCLC.