Solution to Cancer Lies at Molecular Level

BUFFALO, NY—Cancer encompasses more than 100 different diseases and is caused by a series of molecular changes affecting cellular function. “We will find the solution to cancer at the molecular level. There are common patterns in tumor formation and certain keys that are associated with those patterns,” said Carlo Croce, MD, director of the Kimmel Cancer Center, and professor of microbiology and immunology, Thomas Jefferson University, Philadelphia.

One of those keys may be the FHIT gene, which is often inactivated in epithelial tumors, he said at the New Horizons in Cancer Prevention Symposium, hosted by Roswell Park Cancer Institute.

FHIT is most often inactivated in tumors resulting from exposure to a carcinogen, which modifies the way the gene functions. Research suggests that this change in FHIT occurs early in the cancer process. “Since the alteration in the FHIT gene occurs early, this gives us a molecular target to study and possibly change in order to stop the development of malignant cells,” Dr. Croce said.

In a study of preinvasive bronchial dysplasias, various levels of the loss of FHIT expression were noted. In carcinoma in situ, loss of FHIT expression was seen in 100% of tumor cells; in dysplasia, 85%; and in any lesion, 95%.

“Even if we can’t completely stop the development of lung cancer, the identification of the loss of FHIT in bronchial tumors and the potential for a therapy to correct this loss offer an opportunity to eliminate 80% to 90% of precancerous cells. If this continues as we hope, we can make a huge impact on lung tumor incidence,” Dr. Croce said.

In initial studies of methods to replace FHIT function in tumor cells not expressing FHIT, researchers found that restoring the ability to express FHIT normally caused cancer cells to undergo apoptosis.

“This first-look study at replacing the gene offers real hope for a potential therapy. Additional studies will focus on advancing this research into lung cancer and identifying other cancers that may also lose FHIT function before becoming aggressive,” Dr. Croce said.