Dr. William Lockwood, senior scientist at the BC Cancer Research Institute (BCCRI), investigates not only how lung cancer initiates and progresses, but also its response to treatment. He and his team seek to understand the basic biology of lung cancer cells, including which mutations drive the process of cell growth; particularly in people who have never smoked. In doing this research, he and his team at the Lockwood Lab have made exceptional progress in better understanding the genetic basis of lung cancer that could lead to the uncovering of novel compounds that can kill lung cancer.
Hyperactivation
“I am excited for the future of this work," said Dr. Lockwood. “Targeted and immune therapy have been game changing in lung cancer management, drastically improving the outcomes and quality of life for patients. My team and I have continued our new pursuit of killing lung cancers through 'hyperactivation'. We liken this to putting on the gas pedal in tumours as opposed to the brakes, which traditional therapies try to achieve. We think this will help treat lung tumours that do not respond to targeted and immune therapies and may circumvent issues of resistance, a limitation of traditional treatment options."
Dr. Lockwood and team have discovered a target to achieve this through pharmacological inhibition and are now working to develop new inhibitors for clinical use. This outside of the box approach is a paradigm shifting strategy for lung cancer patient care and will be refined in the coming years.
Combating drug resistance
Drug resistance is another problem facing traditional cancer treatments. There are many effective therapies for the clinical treatment of lung cancer and more in the trials stage. However, patients eventually develop drug resistance and the treatment becomes less effective and impacts long-term survival rates.
To that end, Dr. Lockwood and team have characterized a new compound that selectively kills lung cancer cells and not normal lung tissue. Using an innovative approach, they found that this drug inhibits the metabolic function of lung cancer cells, depriving them of essential molecules they need to survive. This vulnerability in lung cancer cells is present in the vast majority of patient tumours.
Using protein targeting and viruses to combat lung cancer
Dr. Lockwood and his team have also worked on two approaches to treat lung cancer caused by EGFR (epidermal growth factor receptor) mutant genes. In the first approach they found a protein, termed GGA2, that EGFR-mutant lung cancers need to survive. By targeting this protein, new treatment methods could kill both drug sensitive and resistant EGFR mutant tumours. In his second approach, the team uncovered how some EGFR-mutant lung cancers 'change their skin' to become resistant to targeted therapies. By understanding how the tumours are able to adapt, the team can work to develop new ways to prevent this form of resistance from occurring.
Lastly, in a year that has been dominated by COVID-19, Dr. Lockwood and his team have discovered a different type of virus, one that typically causes hand, foot and mouth disease but can be engineered to selectively kill lung cancer cells caused by a specific type of mutated gene called KRAS. Mutated KRAS genes cause the majority of lung adenocarcinomas and currently have no approved treatment.
“We now hope to translate these findings towards patient care, aiming to assess gene status in individuals and correlating this with lung cancer risk and developing more suitable formulations of compounds for treatment."
For more lung cancer awareness stories, read the 2020 Research Report (PDF).
