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Los Angeles News, a new preclinical study led by researchers at the Jonsson Comprehensive Cancer Center at UCLA shows that immune checkpoint inhibitors are used to treat patients with aggressive cancers, including patients with melanoma, pancreatic cancer, and colorectal cancer.
Immune checkpoint inhibitors work by reactivating immune cells or T cells that kill tumors, while mutation-targeted therapy kills tumors that contain specific mutations that open cancer-driving pathways, which completely changes the treatment of advanced cancer patients.
Recent studies have shown that combining immune checkpoint inhibitors against PD-1/L1 and MAPK targeted therapy (usually used alone to treat cancer patients) may help overcome treatment resistance
"We already have powerful drugs for advanced cancer in our arsenal," said Roger S.
In this study, published in Cancer Cell, the researchers tested in multiple animal models of human melanoma, pancreatic cancer, and colorectal cancer driven by mutations in common genes such as BRAF, NF1, NRAS, and KRAS.
They unanimously found that only one treatment plan is far superior to other treatments, and revealed molecular and cellular mechanisms to explain why the combination therapy can be based on the sequencing to maximize the therapeutic effect
Dr.
The team also proved that reasonable sequencing of anti-PD-1/L1 therapy before adding MAPK inhibitors can inhibit melanoma brain metastasis and improve the survival rate of mice
Researchers have discovered powerful clonal expansion of T cells in all parts of the body where cancer cells have spread, including the brain
In sequential combination therapy, the team can make tumors more obvious to the body's anti-cancer T cells, and the growth environment of T cells is more suitable for their growth and tumor-killing activities
"Especially in melanoma, we are surprised how effective this therapy can inhibit treatment resistance," Lo said
This research was inspired by clinical observations that gave rise to hypotheses that the team tested in the laboratory
Original Search: Anti-PD-1/L1 lead-In before MAPK inhibitor combination maximizes antitumor immunity and efficacy
