Cancers: The latest mechanism of action for cancer drugs

February 4, 2021 // -- Chris Oostenbrink, a biosynthicist from Vienna, and others recently analyzed for the first time the mechanisms of the cancer antibody drugs nivolumab and pembrolizumab and found that these tiny molecular movements are critical.
the study has been published in the journal Cancer.
(Photo: www.pixabay.com) the body's immune system protects the body from damaged cells such as bacteria, viruses and cancer cells.
specialized immune cells, such as natural killer cells (NK cells), can jointly identify and eliminate these threats.
, these killer cells inadvertently target healthy cells, which can lead to severe autoimmune responses.
this happens, the immune system will take a safety measure called "procedural cell death" (apoptosis).
this condition is triggered when the endogenetic surface molecule PD-L1 binds to a subject expressed on the killer cell PD-molecule.
process, the (immune checkpoint) subject acts like an emergency switch off.
if cells are mistakenly attacked, they produce PD-L1 molecules and reach killer cells, killing them.
cells can also express PD-L1, and these cells bind to checkpoints, causing killer cells to die and tumors to grow.
this is where modern immunotherapy anti-cancer drugs (checkpoint inhibitors) are targeted.
Wolfgang Schreiner of MedUni Vienna Institute of Biosynthtics and Bioinsytics, and Gynaecologists Georg Pfeiler and Heinz K, Director of Obstetrics and Gynaecology, MedUni Vienna The main differences between natural PD-L1 and drugs used to treat various cancers, such as breast cancer, lung cancer and melanoma, were studied in molecular dynamics models through computer simulations by Chris Oostenbrink of Boku Vienna.
and mathematically analyzed the motion of individual atoms and their effects on supercomputer computers.
this way, the smallest difference between the molecular movement of the natural molecule PD-L1 and the pharmaceutical molecule can be determined.
Schreiner explains: "It is almost possible to make accurate mathematical assessments of the "facial expressions" of slow-motion molecules, almost personally.
found that some rings of PD-1 molecules are deformed in different ways, depending on their binding partners.
" these small differences are directed by PD-1 molecules into killer cells and have the desired effect, i.e., although the drug binds to the subject, it does not activate the subject as the natural surface molecule PD-L1 does.
() Source: Modern anti-cancer drugs work via tiny molecular motions Original source: Bernhard Roither et al, Pembrolizumab Induces an Unexpected Solution Change in the CC'-loop of PD-1, Cancers (2020). DOI: 10.3390/cancers13010005