Blood Vessel Markers in Breast Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: A long standing goal of researchers and physicians is to be able to direct therapies directly to the appropriate location in the body. If it were possible to selectively deliver drugs to their intended targets, then many effective, but toxic, drugs could be used more effectively. For example, cancer chemotherapy, which to a large extent relies on highly toxic compounds that are only partially selective for tumor cells, could benefit enormously from selective delivery. Higher concentrations of the agent would be reached in the tumor, and less would go to vulnerable healthy tissues. Similarly, the potential harm from delivering genes into normal cells, which is a serious limitation in gene therapy of cancer (and of other diseases), could be attenuated by better targeting strategies. We have developed a new approach to solve the drug targeting problem.
 
 
 
 
 
 
 
 Tumors initially form as tiny clumps of cells, which are limited in size to 1-2 millimeters. Tumors can escape this size limitation by inducing the growth blood vessels, such that that the vessels keep pace with the growth of the tumor and provide nourishment. Interestingly, there are differences in the composition of the tumor-specific blood vessels from those in other parts of the body. This is especially true for newly produced blood vessels, which have their own special endothelial cell protein surface markers. In contrast, normal blood vessels do not have these growth and tumor-associated surface markers, except when tissue is repaired (i.e., wound healing). 
 
 
 
 
 
 
 
 Our approach is to employ a strategy that recognizes the molecular differences inherent in different types of blood vessels. Protein structure and binding properties are the key vessel signature, since the significant differences in blood vessels are due to unique proteins. For our studies we engineer small pieces of protein, peptides, that are present on viruses, called phage. Thus, the phage will bind to specific blood vessel markers via the peptides in their surface. When injected into the circulation certain subsets of these phage/peptides home to the blood vessels in a tumor. We can begin a study with large 'libraries' of phage/peptides, and then select subsets that bind to tumor vessels. Importantly, these small "homing peptides" can eventually be designed to carry cancer chemotherapy drugs. 
 
 
 
 
 
 
 
 Most recently, we have identified peptides that home selectively to the blood vessels of breast cancer. A novel feature of these peptides is that, unlike our earlier tumor homing peptides, the homing of the new peptides is not related to growth of blood vessels. Rather, the binding sites for these peptides (the receptors) seem to represent a signature that this particular type of a tumor places on its blood vessels. Thus, these peptides may allow us to target drugs into breast cancers, increasing the drug's efficacy and reducing its side effects in a manner that would not interfere with normal tissue healing. A cancer patient could, for example, be recovering from a heart attack, and a treatment that destroys all growing blood vessels could be detrimental to this process, which requires the growth of new blood vessels.
 
 
 
 
 
 
 
 Our aims are to explore a novel strategy for the more efficient targeting of drugs to breast cancer. This will result in enhanced effectiveness for killing tumor cells and will reduce the toxicity that results in so much human suffering from current use of chemotherapeutics.