CUHK Passions and Pursuits

30 I t is through the emerging field of personalized medicine that CUHK professor and oncologist Tony Mok has been improving the treatment and lives of lung-cancer patients. As the lead investigator on two landmark studies, he has helped to establish new approaches to the treatment of lung cancer that can extend the lives of people afflicted by the disease. Professor Mok has been tracking patients with what is known as the epidermal growth factor receptor (EGFR) mutation, an oncogene that can cause normal cells to become tumorous and that results in thousands of lung-cancer cases every year. He has established that it can be more effective to treat advanced lung cancer caused by the EGFR mutation with a pill that a patient can take once a day, without the need for chemotherapy, which is more toxic. In the EGFR mutation, a genetic defect on the receptor causes a malfunction, providing a continuous growth signal to the cancer cell, which then grows uncontrollably. The drug gefitninib, marketed under the name Iressa by AstraZeneca, inhibits an enzyme, tyrosine kinase, which acts as the ‘on’ and ‘off’ switch for the signal. It binds with the tyrosine kinase, and inhibits the enzyme, meaning the signal is no longer sent. Professor Mok oversaw the Iressa Pan-Asia Study, or IPASS, the study that first established the foundation for using personalized, gene-based medicine to treat lung cancer. All patients with adenocarcinoma are now mandated to be tested for the EGFR mutation. The paper from the multinational study led by Professor Mok— ‘Osimertinib or Platinum-Pemetrexed in EGFR T790M–Positive Lung Cancer’—was selected by The New England Journal of Medicine as one of the ‘Notable Articles of 2017’. Following another ground-breaking discovery in Japan, that the re- arrangement of an enzyme known as anaplastic lymphoma kinase or ALK can also cause lung cancer, Professor Mok launched another major study known as PROFILE 1014. Again, the ALK abnormality can be traced through genetic testing. PROFILE 1014 looked into the use of another drug, crizotinib, that inhibits the ALK. The study, conducted with Prof. Benjamin Solomon at the Peter MacCallum Cancer Centre in Melbourne, confirmed the superiority of crizotinib over chemotherapy, findings that came out in the New England Journal of Medicine in 2014. Unlike EGFR, ALK is not a mutation but instead involves the translocation of chromosome 2. What used to be an c c Professor Mok: ‘The whole objective is to convert a fatal lung cancer into a chronic illness.’