Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy
Intratumor heterogeneity leads to different responses to targeted therapies, even within patients whose tumors harbor identical driver oncogenes. This study examined clinical outcomes according to a patient-derived cell (PDC)-based drug sensitivity test in lung cancer patients treated with targeted...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/4/778 |
| _version_ | 1797298656971325440 |
|---|---|
| author | Sunshin Kim Youngjoo Lee Bo Ram Song Hanna Sim Eun Hye Kang Mihwa Hwang Namhee Yu Sehwa Hong Charny Park Beung-Chul Ahn Eun Jin Lim Kum Hui Hwang Seog-Yun Park Jin-Ho Choi Geon Kook Lee Ji-Youn Han |
| author_facet | Sunshin Kim Youngjoo Lee Bo Ram Song Hanna Sim Eun Hye Kang Mihwa Hwang Namhee Yu Sehwa Hong Charny Park Beung-Chul Ahn Eun Jin Lim Kum Hui Hwang Seog-Yun Park Jin-Ho Choi Geon Kook Lee Ji-Youn Han |
| author_sort | Sunshin Kim |
| collection | DOAJ |
| description | Intratumor heterogeneity leads to different responses to targeted therapies, even within patients whose tumors harbor identical driver oncogenes. This study examined clinical outcomes according to a patient-derived cell (PDC)-based drug sensitivity test in lung cancer patients treated with targeted therapies. From 487 lung cancers, 397 PDCs were established with a success rate of 82%. In 139 PDCs from advanced non-small-cell lung cancer (NSCLC) patients receiving targeted therapies, the standardized area under the curve (AUC) values for the drugs was significantly correlated with their tumor response (<i>p</i> = 0.002). Among 59 chemo-naive EGFR/ALK-positive NSCLC patients, the PDC non-responders showed a significantly inferior response rate (RR) and progression-free survival (PFS) for the targeted drugs than the PDC responders (RR, 25% vs. 78%, <i>p</i> = 0.011; median PFS, 3.4 months [95% confidence interval (CI), 2.8–4.1] vs. 11.8 months [95% CI, 6.5–17.0], <i>p</i> < 0.001). Of 25 EGFR-positive NSCLC patients re-challenged with EGFR inhibitors, the PDC responder showed a higher RR than the PDC non-responder (42% vs. 15%). Four patients with wild-type EGFR or uncommon EGFR-mutant NSCLC were treated with EGFR inhibitors based on their favorable PDC response to EGFR inhibitors, and two patients showed dramatic responses. Therefore, the PDC-based drug sensitivity test results were significantly associated with clinical outcomes in patients with EGFR- or ALK-positive NSCLC. It may be helpful for predicting individual heterogenous clinical outcomes beyond genomic alterations. |
| first_indexed | 2024-03-07T22:39:10Z |
| format | Article |
| id | doaj.art-ea6cb74c71e5412a906641852b87c93a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:39:10Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ea6cb74c71e5412a906641852b87c93a2024-02-23T15:11:12ZengMDPI AGCancers2072-66942024-02-0116477810.3390/cancers16040778Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted TherapySunshin Kim0Youngjoo Lee1Bo Ram Song2Hanna Sim3Eun Hye Kang4Mihwa Hwang5Namhee Yu6Sehwa Hong7Charny Park8Beung-Chul Ahn9Eun Jin Lim10Kum Hui Hwang11Seog-Yun Park12Jin-Ho Choi13Geon Kook Lee14Ji-Youn Han15Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaCenter for Lung Cancer, National Cancer Center, Goyang 10408, Republic of KoreaCenter for Lung Cancer, National Cancer Center, Goyang 10408, Republic of KoreaCenter for Lung Cancer, National Cancer Center, Goyang 10408, Republic of KoreaDepartment of Pathology, National Cancer Center, Goyang 10408, Republic of KoreaCenter for Lung Cancer, National Cancer Center, Goyang 10408, Republic of KoreaDepartment of Pathology, National Cancer Center, Goyang 10408, Republic of KoreaResearch Institute, National Cancer Center, Goyang 10408, Republic of KoreaIntratumor heterogeneity leads to different responses to targeted therapies, even within patients whose tumors harbor identical driver oncogenes. This study examined clinical outcomes according to a patient-derived cell (PDC)-based drug sensitivity test in lung cancer patients treated with targeted therapies. From 487 lung cancers, 397 PDCs were established with a success rate of 82%. In 139 PDCs from advanced non-small-cell lung cancer (NSCLC) patients receiving targeted therapies, the standardized area under the curve (AUC) values for the drugs was significantly correlated with their tumor response (<i>p</i> = 0.002). Among 59 chemo-naive EGFR/ALK-positive NSCLC patients, the PDC non-responders showed a significantly inferior response rate (RR) and progression-free survival (PFS) for the targeted drugs than the PDC responders (RR, 25% vs. 78%, <i>p</i> = 0.011; median PFS, 3.4 months [95% confidence interval (CI), 2.8–4.1] vs. 11.8 months [95% CI, 6.5–17.0], <i>p</i> < 0.001). Of 25 EGFR-positive NSCLC patients re-challenged with EGFR inhibitors, the PDC responder showed a higher RR than the PDC non-responder (42% vs. 15%). Four patients with wild-type EGFR or uncommon EGFR-mutant NSCLC were treated with EGFR inhibitors based on their favorable PDC response to EGFR inhibitors, and two patients showed dramatic responses. Therefore, the PDC-based drug sensitivity test results were significantly associated with clinical outcomes in patients with EGFR- or ALK-positive NSCLC. It may be helpful for predicting individual heterogenous clinical outcomes beyond genomic alterations.https://www.mdpi.com/2072-6694/16/4/778patient-derived celltargeted therapyEGFR mutationALK fusionlung cancerpredictive marker |
| spellingShingle | Sunshin Kim Youngjoo Lee Bo Ram Song Hanna Sim Eun Hye Kang Mihwa Hwang Namhee Yu Sehwa Hong Charny Park Beung-Chul Ahn Eun Jin Lim Kum Hui Hwang Seog-Yun Park Jin-Ho Choi Geon Kook Lee Ji-Youn Han Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy Cancers patient-derived cell targeted therapy EGFR mutation ALK fusion lung cancer predictive marker |
| title | Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy |
| title_full | Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy |
| title_fullStr | Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy |
| title_full_unstemmed | Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy |
| title_short | Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy |
| title_sort | drug response of patient derived lung cancer cells predicts clinical outcomes of targeted therapy |
| topic | patient-derived cell targeted therapy EGFR mutation ALK fusion lung cancer predictive marker |
| url | https://www.mdpi.com/2072-6694/16/4/778 |
| work_keys_str_mv | AT sunshinkim drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT youngjoolee drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT boramsong drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT hannasim drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT eunhyekang drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT mihwahwang drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT namheeyu drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT sehwahong drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT charnypark drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT beungchulahn drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT eunjinlim drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT kumhuihwang drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT seogyunpark drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT jinhochoi drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT geonkooklee drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy AT jiyounhan drugresponseofpatientderivedlungcancercellspredictsclinicaloutcomesoftargetedtherapy |