Author of

• 29280

  +

  ES11 - Lung Cancer Plasticity and Drug Resistance (ID 14)

  • Event: WCLC 2019
  • Type: Educational Session
  • Track: Biology
  • Presentations: 1
  • Now Available
  • Moderators:Luca Roz, Nagahiro Saijo
  • Coordinates: 9/08/2019, 15:15 - 16:45, Colorado Springs (1994)

  • 29284

    +

    ES11.04 - Mechanisms for Resistance to TKI and ICI (Now Available) (ID 3214)

    15:15 - 16:45  |  Presenting Author(s): Katerina Politi
    • Abstract
    • Presentation
    • Slides

    Abstract
    

    Targeted therapies and immunotherapies have transformed the treatment landscape for lung cancer over the past 15 years. These therapies are effective in subsets of patients, however, acquired resistance is an impediment to cures. In the case of targeted therapies, acquired resistance occurs in all cases although new generations of targeted therapies delay inevitable relapse. Upon treatment with immune checkpoint inhibitors, data suggest that acquired resistance occurs in ~50% of cases following an initial response to the therapies. However, studies of acquired resistance to these immunotherapies are limited and the exact frequency remains to be determined. Therefore understanding the mechanisms of acquired resistance to targeted therapies and immunotherapies is of critical importance to developing new therapeutic strategies to overcome and prevent the emergence of drug resistance.

    EGFR mutant lung cancer is a paradigm for the use of targeted therapies in this disease. Tyrosine kinase inhibitors (TKIs) are the first line of treatment for EGFR mutant lung cancer and are effective in 70-80% of cases. Acquired resistance to first and second generation inhibitors, like erlotinib, gefitinib and afatinib, most frequently is the result of a secondary mutation in EGFR, EGFR T790M. Third generation TKIs that can inhibit the activity of EGFR T790M-containing mutants were recently developed and one of these, osimertinib, is now approved for the first- and second-line treatment of EGFR mutant lung cancer and is increasingly used in the clinic. Even with osimertinib, acquired resistance occurs and there is a need to understand the mechanisms of resistance to this TKI. We will review current knowledge of acquired resistance to osimertinib and discuss new findings from studies in genetically engineered mouse models, patient-derived xenografts, patient specimens and cell line models.

    In contrast to the extensive knowledge of the mechanisms of acquired resistance to TKIs, very little is known about acquired resistance to immune checkpoint inhibitors. In melanoma, lung cancer and colon cancer, defects in antigen processing and presentation have emerged as a mechanism of acquired resistance to these agents. Defects in this pathway can occur in different ways including loss of specific neoantigens and genetic loss or downregulation of essential components of the pathway like b2-microglobulin. In the presentation, we will discuss known mechanisms of acquired resistance to immune checkpoint inhibitors and new approaches and models that we and others are developing to study this problem.

    Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

    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.