New approaches to treating lung cancer are of great interest, particularly since the disease causes more deaths than any other type of cancer. And common therapies, such as surgery, chemotherapy and radiation, are ineffective in people with advanced stages of the disease. Moreover, according to the Centers for Disease Control and Prevention, lung cancer places a $9 billion burden on the U.S. economy every year.

One new therapy is gaining international attention. In mouse trials, researchers from the Ministry of Education, Science and Technology in Korea have successfully employed a vaporized viral vector to deliver a cancer-inhibiting molecule directly to lung tissue. "Aerosol delivery targets the lungs specifically and represents a noninvasive alternative for targeting genes to the lung," writes Myung-Haing Cho, D.V.M., Ph.D., professor at Seoul National University and principal investigator of the study. "The delivery of genes via aerosol holds promise for the treatment of a broad spectrum of pulmonary disorders and offers numerous advantages over more invasive modes of delivery," says Dr. Cho. The success of the trial is particularly important because in the past, researchers have had difficulty developing mechanisms that are able to effectively deliver gene therapies to lung tissues.

The study involved the targeting of the Akt signaling pathway, an important regulator of cell proliferation and cancer progression. The researchers selected a lentiviral vector, derived from a retrovirus and known for its ability to infect non-dividing cells and result in persistent genetic changes. As they wrote, they "transfected the lentiviral vector with a negative regulator of Akt signaling, carboxyl-terminal modulator protein (CTMP), which would theoretically inhibit Akt signaling, thus suppressing cancer cell proliferation and tumor growth." One third of the mice in the study were exposed to the aerosolized CTMP vector, one-third to the vector alone and one third were untreated. The mice underwent treatments twice a week for four weeks. After that period of time, the researchers discovered that CTMP delivery suppressed lung tumor mass. And in the CTMP-treatment group, the number and volume of tumors were significantly decreased.

"Our results demonstrated that lentivirus-mediated CTMP overexpression suppressed Akt activity and inhibited tumor progression," writes Dr. Cho. "Repeated aerosol gene delivery may provide an effective noninvasive model of gene delivery and understanding the role of CTMP in the multistage lung tumorigenesis may be essential in developing effective therapeutics for lung cancer."

News Release: Vaporized viral vector shows promise in anti-cancer gene therapy  www.eurekalert.org   June 8, 2009