Virtual Library

Start Your Search

Mohammad Shah Alam

Author of

  • +

    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.03-16 - Anlotinib Inhibits Angiogenesis of Refractory Advanced Non-Small Cell Lung Cancer via Blocking CCL2 Expression (ID 12406)

      16:45 - 18:00  |  Author(s): Mohammad Shah Alam

      • Abstract
      • Slides


      Anlotinib has been demonstrated to be effective in prolonging progression free survival (PFS; Anlotinib: 5.37 months vs Placebo: 1.40 months) and overall survival (OS; Anlotinib: 9.63 months vs Placebo: 6.30 months) of refractory advanced Non-Small Cell Lung Cancer (NSCLC) patients in clinical trials. Clinical evidences suggested that Anlotinib-induced anti-tumor efficacy could be attributed to anti-angiogenesis. However, the underlying molecular mechanisms and predictive biomarker of Anlotinib are still unclear.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      437 patients with advanced NSCLC enrolled in clinical study, and 294 patients received Anlotinib therapy. Retrospectively analysis of the Anlotinib-administrated 294 NSCLC patients was performed to screen out underlying biomarker for Anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the anti-tumor molecular mechanism of Anlotinib in vitro. CCL2 levels and their roles in angiogenesis were evaluated by ELISA detection, RT-qPCR quantification, and immunofluorescence assay, in vivo. Changes in serum CCL2 levels were analyzed to reveal the correlation of Anlotinib response between responders and non-responders.

      4c3880bb027f159e801041b1021e88e8 Result

      Anlotinib therapy is more beneficial to prolong OS for NSCLC patients harboring positive driver gene mutations, especially for patients harboring EGFRT790M mutation. Moreover, our data indicated that Anlotinib-induced cell viability downregulation, cell apoptosis induction, cell invasion inhibition, cell cycle arrest, and cell migration inhibition are associated with CCL2 levels in vitro. We demonstrated that Anlotinib inhibits angiogenesis of NCI-H1975 derived xenografts model via inhibiting CCL2 in vivo. Lastly, we found that Anlotinib-induced serum CCL2 level decreases are associated with the benefits of PFS and OS, in refractory advanced NSCLC patients (n = 28).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study reports a novel anti-angiogenesis mechanism of Anlotinib via inhibiting CCL2 in NCI-H1975 derived xenografts model, and suggests the changes in serum CCL2 levels may be used to monitor and predict clinical outcome in Anlotinib-administered refractory advanced NSCLC patients. The biomarker of serum CCL2 alteration may guide precision therapy of Anlotinib for NSCLC patients at third-line or over third-line.


      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.