Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids
The biggest problem with lung cancer organoid (LCO) is that most lung cancer organoids are derived from surgical specimens of early-stage lung cancer patients. In fact, patients who initially need chemotherapy are patients with advanced lung cancer who cannot undergo a surgery. So, making lung organoids from biopsy specimens successfully is an urgent task. The success rate of culturing LCO from biopsy tissues is very low because conventional lung biopsies such as transthoracic needle biopsy and forcep biopsy only get a small amount of lung tissue. The possibility of critical complications such as bleeding and pneumothorax makes it difficult to obtain enough specimens. Overgrowth of normal lung cells in late passages is also a critical problem in LCO and optimized culture conditions for LCO remain to be identified. To overcome the hurdles of lung cancer organoid, we made LCOs from cryobiopsy specimens of all stages of lung cancer patients. Transbronchial cryobiopsy can obtain over 10 times greater volume of tissue compared to bronchoscopic forceps biopsy and it can be applied to even peripheral lesions with radial endobronchial ultrasonography. The success rate of LCO culture was also markedly improved and recapitulated the characteristics of primary tumors. LCOs derived from cryobiopsy specimens can overcome the critical limitations of present lung cancer organoids. We expect that cryobiopsy will be a breakthrough strategy of clinical application of LCO in all stages of lung cancer. Overall design: We performed scRNA-seq on normal (n=1) and cancer (n=1) lung organoids that we established from cryo-biopsy specimens.