PD-L1 Inhibition + MEK Inhibition
MEK is an emerging target in cancer immunotherapy research
MEK is a signaling molecule in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, proliferation, and differentiation.1,2
Emerging research has found MEK signaling can also disrupt a key step in the cancer immunity cycle: cancer cell recognition.3,4
MEK inhibition can increase tumor cell recognition
Targeting MEK can help restore part of the cancer immunity cycle by increasing antigen presentation and tumor cell recognition.4,5
- MEK inhibition upregulates major histocompatibility complex (MHC) class 1 expression, which can increase the presentation of tumor antigens for recognition by CD8+ T cells
- T cells are then able to recognize and kill tumor cells
Targeting MEK and PD-L1 may have a synergistic effect on restoring the body's antitumor immune response
Inhibition of the MEK and PD-L1 pathways is a rational approach that may help invigorate T-cell activity against tumor cells.5,6
Genentech is actively researching the combination of MEK inhibition and PD-L1 inhibition in various tumor types.7,8
PD-L1=programmed death-ligand 1.
- Dhillon AS, Hagan S, Rath O, Kolch W. Oncogene. 2007;26:3279-3290. PMID: 17496922
- Caunt CJ, Sale MJ, Smith PD, Cook SJ. Nat Rev Cancer. 2015;15:577-592. PMID: 26399658
- Chen DS, Mellman I. Nature. 2017;541:321-330. PMID: 28102259
- Brea EJ, Oh CY, Manchado E, et al. Cancer Immunol Res. 2016;4:936-947. PMID: 27680026
- Ebert PJ, Cheung J, Yang Y, et al. Immunity. 2016;44:609-621. PMID: 26944201
- Bendell JC, Kim TW, Goh BC, et al. J Clin Oncol. 2016;34.
- US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02788279. Accessed November 1, 2017.
- US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02322814. Accessed November 1, 2017.
- Chen DS, Mellman I. Immunity. 2013;39:1-10. PMID: 23890059