These are both very effective regimens. This proposal will translate pre-clinical findings showing that MEK inhibitors (MEKi) enhance infiltration of CD8+ T effector cells, prevent their exhaustive apoptotic cell death, and enhance efficacy of anti-PD-L1 Ab in tumor models. MEK Inhibitor. We will conduct an innovative, randomized phase 2 clinical trial to test combined blockade of MEK and PD-L1 in patients with cholangiocarcinoma, and obtain biopsy and … Sci. Our goal is to extend success of immunotherapy to CC, and identify relevant biomarkers for this approach. They examined two approved therapies, an oncolytic herpesvirus and a MEK inhibitor. Immunotherapy with antibodies to programmed death 1 (PD-1) produces lower response rates but with long response duration. The endpoint there has got to be either the second progression or survival, and that's going to take a long time. Sclafani F. MEK and PD-L1 inhibition in colorectal cancer: a burning blaze turning into a flash in the pan [published online April 16, 2019]. Examples of MEK inhibitors include trametinib and binimetinib, and BRAF inhibitors include vemurafenib and dabrafenib. Immunotherapy treatments have been pioneered in the setting of melanoma, and although subsets of patients are able to survive long term, some tumors are resistant. Lancet Oncol . Lancet Oncol . MEK inhibitors are currently being investigated in a variety of settings—a promising example is the MEK inhibitor trametinib, which has been approved for the treatment of patients with BRAF-mutant metastatic melanoma alone or in combination with a BRAF inhibitor [57]. Although these targeted medications have been effective at treating cancers that were previously not amenable to classic chemotherapy, they have all been reported to potentially cause cancer-drug–induced uveitis. Oncogene-targeted therapy with B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors induces a high initial response rate in patients with BRAF V600-mutated melanoma, with a median duration of response of approximately 1 year 1-3.Immunotherapy with antibodies to programmed death 1 (PD-1) produces lower response rates but with long response … 6. In contrast, targeting the MAPK-pathway by selective BRAF and MEK inhibitors induces high response rates, but … Immunotherapy of advanced melanoma with CTLA-4 or PD-1/PD-L1 checkpoint blockade induces in a proportion of patients long durable responses. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF V600E melanoma. Preclinical models suggest that combining BRAF and MEK inhibitors with PD-1 blockade therapy improves antitumor activity4-6, which may provide additional treatment options for patients unlikely to have long-lasting responses to either mode of therapy alone.
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