Lenvatinib resistance mechanism and potential ways to conquer

Abstract

Graphical AbstractIn this review, we summerized the absorption, distribution, metabolism, excretion of lenvatinib in clinic. The lastest mechanism and potential approches to overcome resistance caused by lenvatinib were supplied.

Sporadic Parathyroid Carcinoma Treated With Lenvatinib, Exhibiting a Novel Somatic MEN1 Mutation

“…Meanwhile, resistance to and side effects of MTKIs are common problems in cancer treatment ( 4 ). The drug resistance mechanisms of sorafenib and lenvatinib includes epithelial-mesenchymal transition, DNA damage, ferroptosis, RNA modification, cytokine overexpression, translational modification, and self-target signal pathway ( 21 , 22 ). While using MTKIs like sorafenib or lenvatinib, it is important to monitor for adverse events and adjust doses or discontinue the drug as needed.…”

Strategies and Recent Advances on Improving Efficient Antitumor of Lenvatinib Based on Nanoparticle Delivery System

“…However, LVN is unaffected by pH-elevating agents, race and renal function. 18 High-fat diet, 19 aging, 20 impaired liver function and hepatoprotective drugs 21,22 could also influence steady-state blood concentrations of orally administered LVN, as shown in Figure 1.…”

“…Regardless of other elements determining the pharmacokinetics of LVN, the actual plasma concentration is the most valuable indicator for patients, and it cannot be replaced by other indirect indicators. 18 However, the relative information is limited and inconsistent. Data from the patients with unresectable HCC revealed that the mean trough plasma concentration was approximately 30-40 ng/mL, regardless of the dose of LVN.…”

“…28 Furthermore, LVN can increase CD8+ T cell activity and reduce the number of myeloid-derived suppressor cells (MDSCs), thus also regulating the immune microenvironment. 18,[28][29][30] To obtain the most out of LVN, these antitumor mechanisms are adequately used and strengthened by combination therapy.…”

“…Nanotechnology is booming, and it has the potential to solve the above problems by actively targeting tumor cells, promoting LVN sensitization, controlling harmful tumor microenvironments, overcoming drug resistance, and reducing toxicity. 18 Nano-drug delivery systems (NDDS) have the physicochemical properties of small dimensions, large surface area, and flexible structure, which could make them have the potential as drug carriers. 43 Because of their unique features, NDDS can increase drug stability, optimize body distribution, prolong circulation time, as well as improve drug targeting to increase efficacy and reduce possible side effects from the free drugs.…”