Research Papers:

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

Joaquim Bosch-Barrera _, Elia Sais, Noemí Cañete, Jordi Marruecos, Elisabet Cuyàs, Angel Izquierdo, Rut Porta, Manel Haro, Joan Brunet, Salvador Pedraza and Javier A. Menendez

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Oncotarget. 2016; 7:32006-32014. https://doi.org/10.18632/oncotarget.7900

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Joaquim Bosch-Barrera1,2,3, Elia Sais1, Noemí Cañete2,4, Jordi Marruecos2,5, Elisabet Cuyàs2,6, Angel Izquierdo1,2,3, Rut Porta1,2,3, Manel Haro2,3,7, Joan Brunet1,2,3, Salvador Pedraza2,3,4, Javier A. Menendez2,6

1Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain

2Girona Biomedical Research Institute (IDIBGi), Girona, Spain

3Department of Medical Sciences, Medical School, University of Girona, Girona, Spain

4Department of Radiology, Diagnostic Imaging Institute, Doctor Josep Trueta University Hospital, Girona, Spain

5Department of Radiotherapy, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain

6ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain

7Department of Pneumology, Doctor Josep Trueta University Hospital, Girona, Spain

Correspondence to:

Joaquim Bosch-Barrera, email: [email protected]

Javier A. Menendez, email: [email protected]; [email protected]

Keywords: non-small cell lung cancer, brain metastasis, silibinin, STAT3, Legasil

Received: December 16, 2015     Accepted: February 21, 2016     Published: March 3, 2016


Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.

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