A collaborative research team from Severance Hospital and the Korea Advanced Institute of Science and Technology (KAIST) has uncovered mechanisms that contribute to the early development of resistance to chemotherapy in pancreatic cancer treatment.

Despite advances in the survival rates of other intractable cancers, pancreatic cancer remains a formidable challenge, with the majority of patients diagnosed at an advanced stage, making surgery an option for less than 10 percent. The standard treatment involves chemotherapy drugs such as folfirinox, gemcitabine, and abraxane.

However, these treatments often face the hurdle of early drug resistance, usually within six months, complicating the therapy process.

As a result, understanding the mechanism behind this resistance was crucial for improving treatment outcomes.

The research team, led by Professors Leem Ga-lam and Bang Seung-min of the Department of Gastroenterology, Kang Chang-Moo from the Department of Hepatobiliary and Pancreatic Surgery at Severance Hospital, and Park Jong-Eun at KAIST Graduate School of Medical Science and Engineering, utilized single-cell transcriptomic analysis on surgical tissues from 17 pancreatic cancer patients treated at Severance Hospital between Jan. 2019 and July 2020.

This innovative approach revealed the emergence of chemotherapy-resistant pancreatic cancer cells post-treatment, providing evidence supporting the 'metastasis theory'—the idea that cancer cells evolve to develop resistance to chemotherapy.

Additionally, the study discovered five distinct cell types—Basal-like, Classical, EMT-related, Transitional, and Ductal-associated—with unique characteristics that contribute to drug resistance.

The team believe that this advancement suggests that targeting these specific cell types in drug development could potentially inhibit the development of resistance, thereby enhancing the effectiveness of chemotherapy treatments for pancreatic cancer.

“The principle of early resistance development after chemotherapy treatment for pancreatic cancer has been elucidated,” Professor Leem said. “It is expected that by blocking resistance early due to chemotherapy, the treatment outcomes for pancreatic cancer can be improved.”

Genome Medicine published the results of the study.