SaedNews: Researchers say this new method may help treat patients with certain cancers with minimal side effects.
SaedNews Science and Technology Service Reports:
For some proteins, just a single mutation or change in the DNA instructions means the balance between normal function and cancer development is lost.
According to I.E., despite causing major diseases, these mutated proteins can resemble their normal versions so closely that treatments designed to target the mutated forms can also harm healthy cells.
A new study conducted by researchers at NYU Langone Health and the Perlmutter Cancer Center describes the development of a biologic drug derived from natural biological systems that targets the mutated cancer protein called Epidermal Growth Factor Receptor Number 2 (HER2) without attacking its nearly identical natural counterparts in healthy cells.
New Treatments
While this treatment method is still in early stages, researchers say it could lead to new therapies for cancer patients with HER2 mutations with minimal side effects.
Shohei Koide, head of the research team, says:
"We decided to create an antibody that can detect a single change in 600 amino acid building blocks that form the exposed part of the HER2 protein — something commonly believed to be very difficult."
The fact that we could distinguish a single amino acid change so clearly was astonishing.
When a single amino acid substitution locks the protein in an “always active” state, it can cause cancer by triggering uncontrolled cell division and proliferation.
Saving Healthy Cells
There are several FDA-approved treatments, including Trastuzumab and Pertuzumab, that can treat this type of cancer, but these treatments act at the cellular level on HER2, where only low levels of the mutated HER2 version are present.
Dr. Koide, as the Biological Director of Cancer, says:
"This means we cannot mark cancer cells just by looking at HER2 levels."
Moreover, since some approved treatments cannot differentiate between mutated and normal HER2, they are likely to damage healthy cells that express normal HER2.
Antibodies are large Y-shaped proteins that bind to specific targets and send signals to immune cells.
Treatment Development Process
In a process similar to natural antibody development, researchers subjected antibodies to multiple rounds of mutation and selection, searching for types that recognized mutated HER2 but not the normal version.
By capturing atomic images with cryo-electron microscopy, the team observed how their new antibodies spatially interact with HER2.
However, selective recognition of mutated HER2 variants was only part of developing an effective cancer treatment because antibodies must also work with the immune system to kill cancer cells.
