Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy

摘要: The PI3K pathway is hyperactivated in most cancers, yet the capacity of inhibitors to induce tumor cell death limited. efficacy inhibition can also derive from interference with cancer cells' ability respond stromal signals, as illustrated by approved PI3Kδ inhibitor idelalisib B-cell malignancies. Inhibition leukocyte-enriched or PI3Kγ may unleash antitumor T-cell responses inhibiting regulatory T cells and immune-suppressive myeloid cells. Moreover, angiogenesis be targeted enhance therapy. Future work should therefore explore effects on stroma, addition their cell–intrinsic impact. Significance: extends beyond direct regulation proliferation survival. In malignancies, targeting purges protective microenvironment. we propose that isoform–selective exploited context immunotherapy improve drug immune delivery. Cancer Discov; 6(10); 1090–105. ©2016 AACR.