Recent research has shed light on a mechanism by which an anticancer drug effectively enters cancer cells, revealing that it triggers a process called “outside-in” signaling.
This innovative study explores a new signaling pathway that could potentially enhance the targeted delivery of various therapeutic agents to combat cancer.
Aggressive Cancer and P-cadherin
Aggressive forms of cancer often exhibit elevated levels of P-cadherin, a protein positioned on the cell membrane, making it a prime target for drug development efforts.
The abundance of P-cadherin presented on cancer cells has prompted scientists to focus on this protein when designing new treatments.
Monoclonal Antibodies and P-cadherin Interaction
Monoclonal antibodies designed to recognize and bind to P-cadherin can deliver therapeutic components directly to malignant cells.
However, the specific way these antibodies engage with P-cadherin and promote their entry into the cells has remained somewhat of a mystery until now.
To investigate this interaction, graduate researchers Bin Xie and Shipeng Xu from the University of California, Davis, in collaboration with Professor Sanjeevi Sivasankar, conducted a range of experiments centered on the antibody CQY684 and its relationship with P-cadherin.
Mechanism of Action
P-cadherin functions as a dimer, meaning it pairs up with P-cadherin molecules from adjacent cells.
This dimerization can take on two distinct structural forms: the more relaxed “strand-swap” configuration and a closely bonded variant known as the X-dimer.
The team found that when CQY684 attaches to P-cadherin, it promotes the formation of the X-dimer.
This stable arrangement sets off a signaling cascade that leads to a section of the cell membrane being engulfed as a small vesicle.
As a result, the complex of P-cadherin, the antibody, and the drug is transported to an organelle called the lysosome, where it undergoes degradation.
The researchers emphasized that their exploration reveals an outside-in signaling mechanism that provides valuable insights into how cellular adhesion is regulated.
By understanding how antibodies bind to cadherin, scientists could pave the way for groundbreaking drug designs that leverage this signaling pathway to precisely target and destroy cancer cells.
This discovery could have significant implications for developing new therapeutic strategies, particularly in oncology.
Researchers are now investigating how this mechanism intersects with existing treatments, such as cholesterol drugs and bladder cancer therapies, to enhance their effectiveness.
By integrating these insights, future treatments may offer more precise and targeted approaches for combating aggressive tumors.
Source: ScienceDaily