When the ICGC was established in 2007, researchers set out to profile 50 different cancers of clinical and societal importance across the globe. In Korea, where a quarter of all cancer deaths are from lung cancer, Keunchil Park led the first genomic study of lung squamous cell carcinoma to address the lack of treatment options available for these patients. Every day in practice he sees unmet clinical needs that continue to motivate his research.
Over the past two decades, Keunchil Park has seen firsthand the dramatic shift in the treatment of the most common type of lung cancer, lung adenocarcinoma, based on discoveries from genomic profiling.
“It really is the prototype of the precision oncology,” says Professor Park says from the Innovative Cancer Medicine Institute at the Sungkyunkwan University School of Medicine in Seoul, South Korea.
The introduction of molecularly targeted therapies for lung cancer patients with a mutation in the EGFR gene, he continues, has dramatically improved their survival: “The [median] overall survival now is well over three years [for these patients] and their quality of life is also much better.”
But lung cancer is a disease with many subtypes and Professor Park wants to extend those benefits to his other patients, particularly those with squamous cell carcinoma, the second most prevalent type of lung cancer. “This subtype of non-small cell lung cancer has very little or no progress at all during the past few decades,” he explains. “There are currently no approved targeted therapies.”
To address this, Park led the first genomic study of lung squamous cell carcinoma in an Asian population, using whole exome sequencing to analyze over 100 tumor samples from Korean patients. The study typified the efforts of the ICCG. A new mutation was identified that upon further investigation, Park realized had been missed in the US National Cancer Institute’s Cancer Genome Atlas earlier analysis of squamous cell carcinoma.
“This mutation is not unique to Korean [patients with] squamous cell [carcinoma],” he explains. “It is also found in Caucasian squamous cell [carcinoma] as well. That was our major finding.” The mutation defined a new subset of the disease which can potentially be targeted with molecularly guided therapies and the study emphasized the importance of collating comparative datasets from around the word through open-access data portals, like the ICGC platform.
It also showed that more comparative genomic data was needed to determine whether Korean cancer patients harbor the same spectrum of genetic aberrations that had been so comprehensively described elsewhere, or if the population differs in ways that may influence treatment.
So the pioneering clinician scientist partnered with biotechnology company Illumina to establish the first national genomic database for Korea to study the genomic landscape of common cancers across the country. A centralized lab was used to coordinate the study and expedite testing
“It was a very timely opportunity for me to lead a collaborative nationwide molecular profiling project,” he says, which had not before been possible in Korea.
Park recognized the shared value of the nationwide study that, in time, would profile over 1000 tumor samples from Korean patients at five major cancer institutes. It would standardize workflows and develop the necessary computational infrastructure for future studies; establish technical criteria for using targeted panel sequencing in clinical practice; and enable Korean researchers to participate in global conversations to shape future genomics research.
The benefits continue. With the workflows and infrastructure for high-throughput sequencing now firmly established, Park launched a clinical trial testing potential molecularly guided therapies for a subset of patients with small cell lung cancer who have failed standard care. The trial will screen patients for actionable mutations, test matched therapies and monitor their response to learn which works best.
He also plans to introduce repeat molecular profiling in his clinic to understand how lung cancer evolves as it progresses. “Advanced lung cancer is not curable so the disease will come back after some time. With each repeated failure, there are less and less [treatment] options,” he explains. “We still need more, we need something better.”
For Park, research always starts with a clinical question or the need to improve the care of his patients. Now, like others in the ICGC-ARGO community, he is focused on integrating clinical information with genomic data. He is optimizing an automated database to synthesize in real-time the huge amount of clinical data that is generated in clinics every day with the data from ongoing genomic studies.
“We need to know to best harmonize this clinical data with genomic data,” he says. “That's the major goal of ICGC-ARGO. The [genomic] data, if it has a real clinical implication, has to be utilized in the clinic.”