Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment
The potential of harnessing clinical agents that target oncogene and non-oncogene addiction to enhance ICI sensitivity by converting immunologically ‘cold’ tumours into ‘hot’ lesions is discussed.
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the clinical management of multiple tumours. However, only a few patients respond to ICIs, which has generated considerable interest in the identification of resistance mechanisms. One such mechanism reflects the ability of various oncogenic pathways, as well as stress response pathways required for the survival of transformed cells (a situation commonly referred to as 'non-oncogene addiction'), to support tumour progression not only by providing malignant cells with survival and/or proliferation advantages, but also by establishing immunologically 'cold' tumour microenvironments (TMEs). Thus, both oncogene and non-oncogene addiction stand out as promising targets to robustly inflame the TME and potentially enable superior responses to ICIs.