May 13, 2025
Keio University School of Medicine
A research team led by Associate Professor Hiroyuki Yasuda and Assistant Professor Taro Shinozaki (at the time of the research, currently at the National Hospital Organization Tokyo Medical Center) from the Division of Pulmonary Medicine, Department of Internal Medicine, Assistant Professor Junko Hamamoto from the Division of General Thoracic Surgery, and Professor Toshiro Sato from the Department of Biochemistry, all at the Keio University School of Medicine, has successfully established lung cancer "organoids"—miniature versions of organs—from lung cancer patients. They have identified the cause of recurrence after treatment with anticancer drugs (EGFR tyrosine kinase inhibitors: EGFR-TKIs) and have also identified drugs that may be effective after recurrence.
Lung cancer is classified into several groups according to the type of genetic abnormality (gene mutation) in the cancer cells. Among these, EGFR-mutated lung adenocarcinoma is the largest group, accounting for 20–30% of lung cancers. Multiple EGFR-TKIs have been developed for these cancers and are widely used in clinical practice. However, their effects are not permanent, and in many cases, the drugs become ineffective within one to two years, leading to recurrence. For recurrent lung cancer, effective drugs are limited, and many patients die within one to two years after recurrence. Furthermore, while research into the causes of EGFR-TKI resistance and recurrence (resistance mechanisms) is ongoing, the cause remains unknown in about half of recurrent cases for the most widely used drug, osimertinib (Tagrisso®). Therefore, elucidating these resistance mechanisms and developing subsequent treatments are major challenges.
To clarify the cause of recurrence after EGFR-TKI treatment, the research team established a total of 39 types of organoids from cancer tissues of patients with EGFR-mutated lung adenocarcinoma, both before and after treatment (post-recurrence). Through analysis of these organoids, they discovered for the first time in the world that a "hybrid type," which combines features of both "lung adenocarcinoma" and "lung squamous cell carcinoma," emerges in about a quarter of cases after treatment. Previous studies had shown that recurrence can occur when the lung cancer type changes from "adenocarcinoma" to "squamous cell carcinoma," but recurrence due to a hybrid type was unknown. Furthermore, the research team found that CDK4/6 inhibitor drugs may be effective against these hybrid-type lung cancers. The results of this study are expected to contribute to the development of effective treatments for recurrent lung cancer that has become resistant to EGFR-TKIs. The details of this research were published in the online edition of the British scientific journal Nature Communications on May 11, 2025 (UK time).
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