Cancer Cell: Sequential combination therapy can make the treatment more effective for patients with aggressive cancer!

A new preclinical study led by researchers at the UCLA Johnson Comprehensive Cancer Center showed that immune checkpoint inhibitors are used to treat people with aggressive cancers, including melanoma, pancreatic cancer , and colorectal cancer .

Immune checkpoint inhibitors work by reactivating immune cells or T cells that kill tumors, while mutation-targeted therapy can kill tumors with specific mutations that open the cancer-driving pathway, completely changing the treatment of advanced cancer patients

Recent studies have shown that combining immune checkpoint inhibitors targeting PD-1/L1 with MAPK targeted therapies (usually used alone to treat cancer patients) may help overcome treatment resistance

We already have powerful drugs to fight advanced cancer, and knowing how to dose, sort and combine them reasonably provides doctors with an opportunity to improve the survival rate of patients

In this study published on Cancer Cell, researchers tested different sequential combinations in a variety of animal models of human melanoma, pancreatic cancer, and colorectal cancer.

Graphical summary

They unanimously found that only one program performed far better than others, and revealed molecular and cellular mechanisms to explain why sequencing on top of the combination can maximize the therapeutic effect

The research team stated that the best solution resulted in the highest levels of'good macrophages' in the tumor and the clonal expansion of the T cells responsible for killing the tumor

The team also proved that prior to the addition of MAPK inhibitors, a reasonable order of anti-PD-1/L1 treatment can inhibit melanoma brain metastasis and improve the survival rate of mice

Researchers have detected powerful clonal expansion of T cells in all body parts to which the cancer has spread, including the brain

In the sequential combination scheme, the team was able to make the body's anti-cancer T cells more likely to see tumors and make the environment of T cells more suitable for their growth and tumor-killing activity

Especially in melanoma, the researchers were surprised by the effect of this approach in suppressing treatment resistance.

Based on these laboratory findings, the team has begun testing reasonable sequencing in clinical trials at the University of California, Los Angeles

Reference materials:

Anti-PD-1/L1 lead-in before MAPK inhibitor combination maximizes antitumor immunity and efficacy.