Lay-Language Paper
Customized Molecules for Fighting and Monitoring Cancer in the Human Body
S Lee, M Huang, D Nelson, S Pickup, H Poptani, E Delikatny, J Glickson (glickson@mail.med.upenn.edu),
Molecular Imaging Laboratory
Department of Radiology
University of Pennsylvania
Philadelphia, PA
Author Description of Paper WE-C-ValB-4
Wednesday, August 2, 2006, 11:10 AM
2006 AAPM Meeting, Orlando, FL
Cancer cells express specific receptors on their surfaces. These are like doors that require a specific key to open them. We have been developing large multipurpose molecules called nanoparticles to carry drugs and diagnostic agents to the cancer. Because the body's immune system is geared to reject foreign proteins and other macromolecules, we have chosen particles that naturally occur in the body -- the lipoproteins -- as our vehicles. We target them to specific receptors (doors) by attaching small molecules to their surface ("keys for opening the specific doors"). The trick is to open doors that lead only to cancer cells and not to normal cells. For that we need to know about the specific "keys" that lead only to cancer cells. Many such "keys" or unique "signatures of cancer" have now been identified for breast cancer, prostate cancer, ovarian cancer, etc. We are targeting all of them. Our payloads consist of cancer drugs like taxol, photodynamic agents that produce toxic chemicals when specific wavelengths of light are directed at the tumors, and fluorescent molecules that light up when they are irradiated with specific wavelengths of light in the infrared.
The next family of molecules we are developing are molecules that enter cells through the glucose transport system. Cancer cells generally have a high requirement for glucose, a molecule that is essential for both energy production and replication of the cancer. We take advantage of this unique "sweet tooth of cancer" to use the glucose transport system to deliver agents that will either facilitate detection of the cancer cells or will kill the cancer cell. One class of molecules that we are producing is metal atoms attached to a "glucose-like" molecule. These metal atoms are easily detected by MRI. Other agents that we deliver by this pathway are inactive molecules that break down to generate highly toxic cancer drugs, and still other molecules are photodynamic therapy agents that produce agents that kill the cell once a specific wavelength of light in the infrared region of the spectrum irradiates the cell. Infrared light is used because it can penetrate deep into tissues of the body.
The third class of agents that we are developing is called "molecular beacons." These beacons literally light up or are activated once they encounter specific molecules in the cancer cells. One class of beacons is activated by genetic messages that cancer cells produce called messenger RNAs. Other beacons are specific classes of molecules or enzymes that the cancer produces; these enzymes catalyze or speed up specific chemical reactions. These include enzymes that are produced when the cancer cell decides to commit suicide via a process called apoptosis (programmed cell death). In some instances our beacons simply produce a detectable fluorescent signal that tells us that a specific cancer cell is present or that apoptosis is taking place in that cancer cell. Other agents are used to kill the cancer cell or "convince" it to go into apoptosis. In short, these beacons are "smart agents" that emit no signal until they encounter their specific target in the cancer cell. They emit the signal or produce the chemical reaction selectively in the cancer cell while leaving normal cells alone.
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