Genetic breakthrough in lung cancer

By Dr. Ananya Mandal, MDDec 16 2010

Genetic markers that can tell how long a person with non-small cell lung cancer would survive have been identified by U.S. researchers.

For the study the team studied samples of lung tumors and nearby healthy lung tissue from 30 patients and examined the samples for the presence of messenger ribonucleic acid (mRNA) associated with 48 known genes for molecules called nuclear hormone receptors. Then they compared the active genes with patient outcomes and found that the expression of genes for certain nuclear hormone receptors helped predict patient survival.

Now it is evident that patients with two specific nuclear hormone receptors in their tumor tissue lived the longest. These were the short heterodimer partner and the progesterone receptor.

Study co-lead author Dr. David Mangelsdorf, chairman of pharmacology at the University of Texas Southwestern Medical Center said, “Patient responses to cancer treatment vary widely and often depend on subtle biological differences among tumors…These findings are important because the ability to determine which genes are being expressed in each person’s tumor, as well as a patient's likely survival time, can guide physicians to the most effective and appropriate personalized treatments.”

The study was published in the Dec. 14 edition of the journal PLoS Medicine.

In another breakthrough Australian and international researchers from Germany and the US have found a gene mutation linked to squamous cell lung cancer. This is the most difficult to treat cancer there is. At present there are drugs that can block this gene. This study means clinical trials using the drugs will start next year to find out if they can be safely used in people with squamous cell lung cancer.

Initial laboratory studies have been successful on mice. This drug was found to shrink the mice’s tumours significantly. Further safety and efficacy results in humans would mean huge advance because lung cancer is generally one of the hardest malignancies to treat, as well as one of the most common. According to a latest report from the Australian Institute of Health and Welfare, lung cancer was the sixth-most common cancer in 2007, with 9703 diagnoses. But it was by far the most deadly, claiming 7,626 lives in that year.

According to director of surgical oncology at St Vincent's Hospital in Melbourne and head of the Australian research team, Gavin Wright, “I don’t think it’s hyperbole to say this is probably the biggest finding in lung cancer research to date… This cancer happens in patients for whom we really don’t have anything, apart from chemotherapy.”

The team studied 1000 tumour samples, including about 300 from Australia, which were then genetically analysed. Of these, they found 155 cases of squamous cell carcinoma in which the cells had far too many copies of a particular gene, called FGFR1, which plays an important role in healing. This gene is activated in a normal cell after an injury, and causes cells temporarily to sprout a receptor which, when activated by a hormone, causes the cell to divide and create new tissue to heal the injury. This mechanism goes out of control in the cancer said Dr. Wright. The two drugs work by binding to the receptors, starving the cells of the stimulation they need and triggering cell death. It appeared that up to 25 per cent of squamous cell carcinomas featured excess copies of the gene.

The study was published in the journal Science Translational Medicine.

Cancer Council Australia chief executive Ian Olver said, “Chemotherapy has been very disappointing in lung cancer in general - to have a targeted therapy in squamous cell lung cancer would be very important.” Dr Marie-Liesse Asselin-Labat, a scientist based in the Walter and Eliza Hall Institute of Medical Research’s stem cell and cancer unit also said that this breakthrough would help thousands across the globe and added, “It’s very exciting work.”