An Approach Towards Personalised Treatment for Lung Cancer Patients
Lung cancer is a major cause of death throughout the world with 1.3 million new cases diagnosed every year. The overall survival rate of lung cancer patients is about 16% within five years. Lung cancer occurs due to uncontrolled growth of aberrant cells across the epithelial lining of the breathing tubes and surface of the lungs. Main causes of lung cancer include cigarette smoking, which is responsible for 90% of cases, passive smoking and exposure to asbestos fibres.
Since a major category of lung cancer, non-small cell lung carcinoma (NSCLC), has subtypes with complex patterns of mutations in different genes, treatment is largely ineffective. Pharmaceuticals are typically targeted to individual proteins - for example, some drugs target epidermal growth factor receptors (EGFRs) to block EGF attachment. Moreover, tumours with similar clinical characteristics (location, pathology, size, stage) may respond differently to the same drug.
Pathway-targeted chemotherapeutic agents are new, more effective molecules for lung cancer treatment. A protein kinase inhibitor, AZD6244, is recommended for treating advanced NSCLC, where it inhibits mitogen-activated protein kinase (MEK) in a well-studied cellular survival pathway to cause apoptosis, thus killing off the cancer cells.
AZD6244 seems to be a godsend for some patients but not all NSCLC cases are sensitive to this drug. Scientists now think they know why.
One of the observable differences between AZD6244-sensitive cells and their insensitive counterparts is the high levels of phosphorylated AKT. AKT is activated by phosphorylation to inhibit cell apoptosis through a separate pathway. Since AZD6244 and AKT are involved in two parallel pathways, AZD6244 does not work on patients with abnormal constitutively active (phosphorylated) AKT.
The phosphorylation of AKT is negatively regulated by the phosphatase PTEN. Thus, an abnormally low level of expression of PTEN indicates the presence of constitutively active AKT, which leads to insensitivity to AZD6244.
Using SynaProbe™, oligonucleotide probes can be designed to evaluate the level of expression of PTEN in patients for quick prognosis of drug sensitivity. With this, a more personalised cancer treatment becomes possible, thus reducing the chances of erroneous prescriptions of drugs and improving more lives through the delivery of appropriate treatments. Instead of grasping at straws through trials with different therapeutic drugs, more lung cancer patients can now see hope in the near future.