ABSTRACT
Glioblastoma multiforme (GBM) is the most common and aggressive malignancy of the central nervous system. Treatment usually involves a combination of surgical resection, chemotherapy, and radiotherapy, but ultimately this condition is incurable. Besides the dismal prognosis of GBM, financial factors have also presented challenges for advancing treatments. Taking into consideration the high cost of developing new anticancer drugs as well as the fact that GBM is a rare disease, thus further limiting financial incentive for drug development, it becomes obvious that there has been growing interest for repurposing candidates. One of the most promising drugs to repurpose for treating GBM is disulfiram (DSF). DSF is a relatively nontoxic drug used for more than sixty years in the treatment of chronic alcoholism with the ability to readily cross the blood-brain barrier. Repurposing DSF for use as an anticancer drug in general has recently become of interest because of its preclinically described anticancer effects against various human cancers. Interestingly, a number of these effects were shown to be copper (Cu)-dependent. The purpose of this paper was to review the existing literature surrounding preclinical and clinical data on the effects of DSF -alone or in combination with Cu- in GBM. In addition, we present the first case of a GBM patient safely treated with DSF/Cu combination along with standard therapy exhibiting remarkably increased progression-free (PFS) and overall survival (OS).
Subject(s)
Acetaldehyde Dehydrogenase Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Copper/therapeutic use , Disulfiram/therapeutic use , Glioblastoma/drug therapy , Trace Elements/therapeutic use , Acetaldehyde Dehydrogenase Inhibitors/pharmacology , Adult , Antineoplastic Agents/pharmacology , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Copper/pharmacology , Disulfiram/pharmacology , Glioblastoma/mortality , Glioblastoma/pathology , Humans , Male , Survival Analysis , Trace Elements/pharmacologyABSTRACT
Metastatic pancreatic adenocarcinoma confers a poor prognosis. Even with recent advances in the treatment of this disease with the introduction of two modestly effective chemotherapy regimens, complete responses are still very rare. Moreover, there are no published data on how to further manage the patients who achieve a sustained remission following treatment. Herein, we report the case of a patient with metastatic pancreatic adenocarcinoma who achieved a complete response lasting for more than three years after receiving induction chemotherapy with FOLFIRINOX followed by maintenance with FOLFIRI.
