Engineering Molecules to Track and Attack Cancer

Most of today's anti-cancer drugs are far from specific in attacking tumors. Rather, they are poisons that tend to kill cancer cells more than normal cells. Thus, besides failing to be specifically deadly to cancers, they can cause severe side effects.

Fortunately, cancer researchers are rapidly progressing to more targeted treatments, and AIRC scientists are pioneering such new approaches, as well as diagnostic tracers that more effectively reveal cancers.

For example, AIRC researchers are developing peptoids as basic targeting molecules for diagnosing and treating cancers. Peptoids are slight molecular rearrangements of peptides, short amino acid chains that are fundamental components of cells. This subtle structural difference gives peptoids an enormous advantage as biologically amenable synthetic molecules, as well as carriers of molecular cargo into the cell. Unlike peptides, they are ignored by the body's protective immune system and can circulate in the bloodstream without being degraded. However, they are like peptides in that they readily bind to and are absorbed by the cells that they target.

The researchers are creating libraries of hundreds of thousands of peptoids and screening them to find those that target cancer cells. And, they are developing techniques to attach to these peptoids cancer-killing molecules and MRI imaging agents for cancer diagnosis.

Other AIRC researchers are developing methods to use sub-microscopic nanoparticles called lipoproteins, as well as lipid bubbles called liposomes, to target drugs to liver cancer cells (Ian Corbin). Since lipoproteins are the usual way the body delivers lipids to cells, they are readily absorbed by cells. And since they are natural components of the bloodstream, they are not attacked and degraded by the body's defense mechanism.

The researchers are also engineering synthetic nanoparticles called dendimers to target and deliver MRI imaging molecules to liver cancers (Corbin, Udugamasooriya). Their aim is to design dendimers that could enable clinicians to distinguish liver cancers from noncancerous cirrhotic nodules.

New PET Tracers

Researchers are also developing new tracers to image prostate cancer and pancreatic cells in the analytical techniques positron emission tomography (PET) and single photon emission computed tomography (SPECT) (Xiankai Sun).

In PET, a biologically active radioactive tracer is injected into the body and its tissue concentration mapped by detecting gamma rays that arise from tracer-emitted positrons annihilating with electrons. The analytical technique SPECT also involves detecting gamma rays, but they are directly emitted by a different type of radioactive tracer. In both techniques, mapping of emissions enables construction of images showing real-time tracer distribution in vivo.

These new PET and SPECT imaging probes are based on versatile molecular "scaffolds" that carry a radiolabel, onto which could be attached a variety of biomolecules of interest that target a particular cell or biological process. The researchers are developing imaging probes to reveal prostate cancer metastases and pancreatic beta cells, to enable monitoring of the progression of diabetes and its treatment.

Other AIRC researchers are developing techniques to explore copper metabolism in the body non-invasively with PET (Fangyu Peng). They are using the 64copper radioisotope as a PET tracer to explore copper's role in liver and prostate cancers, as well as in Alzheimer's disease, neuroinflammatory diseases, and the genetic disorder Wilson's disease. Their cancer studies aim at determining whether copper metabolism can be a useful imaging biomarker for cancers, as well as the basis for possible new treatments.