Novel Combination Therapy --- overcome mTOR drug resistance in AML
Hi friends, just sharing the following:
How novel combos could overcome resistance to targeted drugs in leukemia, solid tumors and more
Drugs that target cancer-causing genes have proven effective in many tumor types, but patients often become resistant to them.
Combination therapies could be key to overcoming this problem, and two academic groups recently released promising preclinical research on two such combos.
A team at Cincinnati Children's Hospital Medical Center focused on resistance to mTOR inhibitors in patients with relapsed acute myeloid leukemia (AML).
These drugs, which include rapamycin and several second- and third-generation mTOR inhibitors, are effective in many tumor types but have been disappointing in AML.
The researchers discovered that hemopoietic stem cells in bone marrow respond to the loss of mTOR by activating an alternate protein-signaling pathway that allows leukemia cells to escape treatment.
Inhibiting three other genes by combining mTOR blockers with drugs that are already in clinical trials could counteract resistance, they reported in the journal Proceedings of the National Academy of Sciences.
The UCLA researchers found in preclinical studies that combining two small-molecule drugs that inhibit MEK and RAF suppresses the MAPK pathway.
They believe the combination could hold promise in some aggressive subtypes of melanoma as well as lung, pancreatic and colon cancers, they reported in Cancer Discovery.
Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity
Accepted November 23, 2020