May 1, 2025
Keio University School of Medicine
Japan Science and Technology Agency (JST)
A research team led by Associate Professor Hiroyuki Yasuda of the Department of Internal Medicine (Pulmonology), Keio University School of Medicine; Takahiro Fukushima (a graduate student) of the university's Graduate School of Medicine; and Professor Toshiro Sato of the university's Department of Biochemistry has established "organoids" from 33 patients with small-cell lung cancer. They discovered that some small-cell lung cancers (the non-neuroendocrine subtype) are highly dependent on a growth factor called IGF-1 for proliferation and that inhibitors of the IGF-1 receptor, IGF1R, show potential as a new therapeutic agent.
Small-cell lung cancer is a disease for which the pathophysiology is not well understood and effective treatments are limited. The five-year survival rate for patients with inoperable small-cell lung cancer is less than 10%, making it a prime example of an intractable cancer.
The research team established 40 types of small-cell lung cancer organoids from the tissues of 33 patients. In recent years, it has been found that small-cell lung cancer can be classified into four subtypes based on gene expression patterns (ASCL1, NEUROD1, POU2F3, and YAP1), raising hopes for the establishment of specific, effective treatments for each subtype. The organoids established by the research team included all four of these subtypes. They found that the non-neuroendocrine subtypes (POU2F3 and YAP1), which account for about 30% of all cases, proliferate in response to stimulation by IGF-1 (insulin-like growth factor). Furthermore, using animal models, the team discovered that treatment with inhibitors of the IGF-1 receptor, IGF1R (IGF1R inhibitors), is effective for these subtypes of small-cell lung cancer. This research is expected to lead to the development of new therapeutic strategies (personalized medicine) using IGF1R inhibitors for small-cell lung cancer, a major intractable cancer with limited effective treatment options.
The details of these research findings were published online in the British scientific journal Nature Cancer on April 30, 2025 (UK time).
For the full press release, please see below.