Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates

Abstract

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage of the disease. Current chemotherapy options are unsatisfactory and there is an urgent need for more effective and less toxic drugs to improve the dismal PC therapy. Repurposing of non-oncology drugs in PC treatment represents a very promising therapeutic option and different compounds are currently being considered as candidates for repurposing in the treatment of this tumor. In this review, we provide an update on some of the most promising FDA-approved, non-oncology, repurposed drug candidates that show prominent clinical and preclinical data in pancreatic cancer. We also focus on proposed mechanisms of action and known molecular targets that they modulate in PC. Furthermore, we provide an explorative bioinformatic analysis, which suggests that some of the PC repurposed drug candidates have additional, unexplored, oncology-relevant targets. Finally, we discuss recent developments regarding the immunomodulatory role displayed by some of these drugs, which may expand their potential application in synergy with approved anticancer immunomodulatory agents that are mostly ineffective as single agents in PC.

Repurposed Effect of 177Lu-DOTATATE in the Treatment of Mantle Cell Lymphoma

“…Driven by the advancements in discovering the genetic and epigenetic alterations of tumor cells, this promising approach is expected to provide novel pharmacological agents that overpass the resistance to conventional therapy that is expressed in multiple cancers [ 15 , 16 ]. The repurposed effect of many medications has been studied in colorectal cancer [ 17 ], pancreatic cancer [ 18 ], and brain tumors [ 19 , 20 ]. Moreover, non-Hodgkin lymphoma has also been targeted in drug repurposing studies.…”

Transcriptomics, metabolomics, and in silico drug predictions to prevent or treat liver damage in young and aged burn victims

“…Our approach via the expression data analysis by Cmap was previously used to predict targeted combination treatment for pancreatic cancer successfully 54,55 . Thus, we expect that some of the predicted drugs will prove to be bene cial for burn victims.…”

The effect of heterocyclic substituent at C-3 position of 1-(4-methyl-piperazin-1-yl)isoquinolines on their anticancer activity

“…At that, pharmacological inhibition of nitric oxide synthesis reduces the antitumor activity of FAA [20]. Moreover, the growth inhibition matrix of this compound moderately correlated with Dihydrolenperone, being a haloperidol analog, appears to act mainly through the blockade of the dopamine D2 receptor leading to inhibition of сancer cell proliferation [23]. At the same time, its cytostatic activity is also moderately correlated with O6-methylguanine, leading to the formation of Guanine -Adenosine transi- * GI 50 (growth inhibitory activity) -concentration of the compound causing 50 % decrease in net cell growth; TGI (cytosta tic activity) -concentration of the compound resulting in total growth inhibition; LC 50 (cytotoxic activity) -concentration of the compound causing net 50 % loss of initial cells at the end of the incubation period of 48 h tion mutations, a known mechanism of human oncogene activation and tumor suppressor gene inactivation [24,25].…”