The TSP researchers uncovered a total of 57 genomic changes that occur frequently in lung cancer patients. Of these changes, more than 40 appear to be associated with genes not previously known to be involved in lung adenocarcinoma. More research is needed to precisely identify and characterize these genes, but researchers are excited by the possibility that their findings may suggest new ways of attacking this deadly cancer. The most common abnormality identified by the TSP team involves a region on chromosome 14 that encompasses two known genes, neither of which had been previously associated with cancer. Through additional studies in cancer cells, the researchers discovered that one of the genes, NKX2.1, influences cancer cell growth. NKX2.1 normally acts as a master regulator that controls the activity of other key genes in cells lining the lungs’ tiny air sacs, called alveoli.
Patients with coactivation of TTF-1 and NKX2–8 pathways appears to be resistant to standard cisplatin therapy, suggesting the need for alternative therapies in this cohort of high-risk patients. NKX2 is known as a marker of poor prognosis in lung cancer.
Craig Venter, a biotechnology pioneer, is usually a fan of brash upstarts. A decade ago he upstaged the boffins of the official Human Genome Project by privately sequencing his own genome faster and more cheaply. But he remains sceptical about analysing only the SNPs. He wants to see whole genomes sequenced because “we don’t yet know which parts of the genome are medically relevant.”
Rapalogs may be more effective in combination with other anticancer agents, including chemotherapy and targeted therapies. It is increasingly apparent that the mTOR signaling network is quite complex, and rapamycin treatment leads to different signaling responses in different cell types. A better understanding of mTOR signaling, the mechanism of action of rapamycin, and the identification of biomarkers of response will lead to more optimal targeting of this pathway for cancer therapy.
The investigators found that MCL had the unfortunate characteristics of being incurable as with indolent lymphomas, yet often rapidly progressive, similar to aggressive histologies. Median overall survival (OS) cited in these early series was in the range of 2 to 4 years, prompting several groups to propose novel therapeutic approaches to improve patient outcomes.