Two Possible Strategies for Drug Modification of Gemcitabine and Future Contributions to Personalized Medicine

Abstract

Drug repurposing is an emerging strategy, which uses already approved drugs for new medical indications. One such drug is gemcitabine, an anticancer drug that only works at high doses since a portion is deactivated in the serum, which causes toxicity. In this review, two methods were discussed that could improve the anticancer effect of gemcitabine. The first is a chemical modification by conjugation with cell-penetrating peptides, namely penetratin, pVEC, and different kinds of CPP6, which mostly all showed an increased anticancer effect. The other method is combining gemcitabine with repurposed drugs, namely itraconazole, which also showed great cancer cell inhibition growth. Besides these two strategies, physiologically based pharmacokinetic models (PBPK models) are also the key for predicting drug distribution based on physiological data, which is very important for personalized medicine, so that the correct drug and dosage regimen can be administered according to each patient’s physiology. Taking all of this into consideration, it is believed that gemcitabine can be repurposed to have better anticancer effects.

Design of the New Closo-Dodecarborate-Containing Gemcitabine Analogue for the Albumin-Based Theranostics Composition

“…Conjugates with a modification at the 5’-hydroxyl group are much more stable in blood plasma and undergo metabolic transformations mainly inside the cell [ 36 ]. However, the peculiarities of the cytosine derivative’s metabolism also make it possible to use the heterocyclic base exocyclic amino group for modification [ 37 ]. The majority of effective prodrugs with improved pharmacodynamic and kinetic properties have been obtained precisely by modifying the amino group of gemcitabine.…”

Selenization of Small Molecule Drugs: A New Player on the Board

“…Worth mentioning is the case of selenocyanate functionality, which has been used to modify several drugs including temozolomide (40), tepotinib (46−48), different NSAIDs (107, 110, 111, 113, 115−121), or biotin (122,124). This functional group is standardly used as a selenol precursor given the instability of the latter.…”

“…To surmount these limitations, several strategies have been proposed, such as the chemical modification of the parent compound to yield different prodrugs. 124,125 Given the prominent role of Se derivatives as feasible antitumoral agents, a novel Se prodrug of Gem (Figure 7) has been evaluated in several cancer cell lines and the results are summarized in Table 10. 103 According to the results, 38 exhibited a remarkably enhanced activity in all the tumoral cell lines, while a shrinkage in the cytotoxicity in noncancerous cells can be observed compared to the unmodified drug.…”

Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review

“…Gemcitabine, an analog of cytosine arabinoside, is an anti-tumor drug combating a wide range of diseases [ 36 ]. Gemcitabine has been used as a combination chemotherapy regimen for pancreatic cancer [ 37 ], BCa [ 38 ], non-small cell lung cancer (NSCLC) [ 39 ], biliary tract cancer [ 40 ], and cervical cancer [ 41 ].…”