Human Cells Develop Resistance to RNAi

Researchers have discovered that RNA interference (RNAi), a technology that uses a naturally occurring process to silence genes, may stop working in some cells after a period of time. RNAi is used to study gene function and has potential for treating some diseases.

The reported phenomenon appears similar to that of bacteria developing resistance to certain antibiotics after prolonged use, says lead researcher Dr. Zhi-Ming Zheng of NCI's CCR. The findings raise questions about RNAi's ability to treat diseases that require the silencing of genes over the long term.

"We were initially very surprised by the results," says Dr. Zheng. His team observed the effect several years ago while testing a short hairpin RNA (shRNA) - a mediator of RNAi - designed to silence two cancer-causing genes in human papillomavirus 16, which contributes to the development of cervical cancers.

The shRNA was effective in cancer cells from cervical cancer patients at first, but then stopped working, although it continued to be present. Further tests showed that no mutations had developed, according to findings published in the December 12 online edition of Oncogene. The researchers suggest that resistant cells may have produced a protein that interacts with an RNA molecule processed from the shRNA, preventing the silencing of targeted genes.

Chest X-Rays Detect Early Lung Cancer

Screening for lung cancer with chest x-rays can detect early lung cancer, but it also produces many false-positive test results which cause needless extra tests, according to preliminary results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The report appears in the December 21 Journal of the National Cancer Institute.

"There is no accepted early screening technique for lung cancer," says Dr. Chris Berg, the NCI investigator who leads the PLCO trial. "The PLCO trial will show if chest x-rays, by catching lung cancer when it is still operable, can reduce the death rate from lung cancer."

Of the 67,038 men and women who received a baseline chest x-ray upon entering the trial, 5,991 (8.9 percent) had abnormal results that required follow-up. After undergoing additional tests, 126 (2.1 percent of the 5,991 participants with abnormal x-rays) were diagnosed with lung cancer.

"The positive predictive value was low," says Berg. "That means there were a lot of false-positives on the initial x-rays. If you get a positive result from a chest x-ray, the message is 'Don't panic.'" Berg notes that tissue variations and other benign factors can resemble tumors on an x-ray.

Of the cancers detected, 44 percent were stage I, meaning those patients were good candidates for surgery.

The group that received initial chest x-rays is being tracked alongside a control group of equal size that did not receive screening chest x-rays. Future analysis will reveal if the intervention group has a lower lung cancer mortality rate than the control group.

A separate NCI study, the National Lung Screening Trial, is under way comparing spiral CT with chest x-rays to see if that test might be better at reducing deaths from lung cancer.

Health Insurance and Quality of Cancer Treatment

Evidence-based treatment guidelines exist for almost all common types of cancer. However, many studies have noted disparities in the receipt of guidelines-based treatment, often along lines such as race, economic status, and age. A study by NCI's Division of Cancer Control and Population Sciences (DCCPS) published in the December 20 Journal of Clinical Oncology examined whether the receipt of guidelines-based treatment is also affected by the type of medical insurance held by patients. The study was based on a sample of more than 7,000 patients identified through the Surveillance, Epidemiology, and End Results (SEER) registries.

The investigators examined the association between treatment received and insurance status - private insurance, any Medicaid, Medicare only, or no insurance - for 10 common cancers with established evidence-based treatment guidelines. They also adjusted for other clinical and non-clinical factors such as cancer stage at diagnosis, comorbidities, age, race, and marital status.

Levels of guidelines-based treatment proved to be lower than expected for all groups, but were significantly lower for patients who depended on Medicare or Medicaid alone for insurance. Also of particular note is that non-Hispanic black patients with Medicaid were significantly less likely than other groups to receive guidelines-based treatment, with only half receiving recommended therapy.

The investigators concluded that health insurance is one of many important variables that influence the receipt of guidelines-based therapy. In a follow-up study, they plan to examine how insurance status affects survival after cancer diagnosis.