Caprelsa (vandetanib)

The combination of selpercatinib and cemiplimab was possible, with no new safety signals observed.

P1, N=151, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Oct 2025 | Trial primary completion date: May 2026 --> Oct 2025

Ponatinib, regorafenib, and vandetanib are FDA-approved VEGFR, Tie2, and Ephrin receptor blockers used in the treatment of various malignancies. Other disorders characterized by aberrant angiogenesis include diabetic retinopathies and neovascular age-related macular degeneration.

Moreover, the MTT viability test for compounds 9a, 9b, and 9c demonstrated less cytotoxicity against normal fibroblast cells (WI38), revealing enhanced safety profiles with IC50 values of 28.04, 219.79, and 43.77 μM, respectively, compared to Sorafenib (IC50 = 26 μM). Enzyme inhibition assays revealed that compounds 9a-c effectively inhibited EGFR and VEGFR-2, confirming the multi-targeting potential of this series of compounds.

This study provides molecular-level insights into the structural and photophysical origins of vandetanib's photosensitivity. The findings improve understanding of its adverse effects and can inform the safer design of EGFR-targeting drugs with reduced phototoxic risks.

Molecularly targeted therapies constitute the cornerstone of current strategies, with vemurafenib inhibiting BRAF/MEK in PTC, sorafenib acting as a multikinase suppressor in FTC, vandetanib blocking RET in MTC and berberine-doxorubicin combinations overcoming chemoresistance in ATC. Metabolic interventions, including metformin for glucose modulation in PTC and novel delivery systems such as micelle-encapsulated AB3 for MTC, demonstrate translational potential. The present review summarizes molecular mechanisms, diagnostic tools and emerging therapies while emphasizing the necessity of subtype-specific approaches to improve clinical outcomes in thyroid oncology.

And dacomitinib, regorafenib, fruquintinib, vandetanib, and panitumumab were the top 5 drugs with high risk. Non-antitumor drugs were all moderate risk, involving atorvastatin, zoledronic acid, amiodarone hydrochloride, lithium, and teduglutide...The number of related adverse event reports increased year by year. The results of this study provided the relevant basis for pharmacovigilance, and provided the basis for strengthening drug safety and making correct drug decision in clinical practice.

Pyrazolines 5d and 6a revealed broad-spectrum cytotoxic activities and potent EGFR inhibition with IC50 values of 2.30 µM and 1.47 µM, respectively, in comparison to Vandetanib (IC50 = 0.5 µM) and Gefitinib (IC50 = 0.04 µM). According to predictive models of oral bioavailability and drug-likeness, pyrazolines 5d and 6a are expected to be bioavailable and drug-like compounds. Pyrazolines 5d and 6a are novel EGFR inhibitors with a broad-spectrum anti-cancer activity, and 6a has off-target antileukemic effect.

Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g., V804L/M, G810C/S/R), both of which limit their clinical application...To overcome drug resistance, the design strategies of novel inhibitors focus on multi-target inhibition (such as PLM-101 targeting RET/YES1/FLT3, TPX-0046 targeting RET/SRC), structural optimization (such as helical ring derivatives enhancing binding stability), and natural compound screening (such as ZINC series molecules)...For instance, selpercatinib combined with crizotinib can inhibit MET amplification-driven resistance, while arsenic trioxide combined with pralsetinib restores sensitivity by inhibiting the HH-Gli pathway. Current clinical trials show that novel RET inhibitors such as SY-5007 have a significant objective response rate in advanced RET fusion-positive non-small cell lung cancer and are safer than traditional drugs. In the future, it is necessary to further develop broad-spectrum mutation coverage and highly selective inhibitors, and explore individualized combination treatment regimens to improve prognosis. This article systematically reviews the progress, resistance mechanisms and coping strategies of RET-targeted therapy, providing a theoretical basis and direction for the development of precision anti-cancer drugs.

Multikinase inhibitors (MKIs) such as sorafenib, lenvatinib, vandetanib and cabozantinib have demonstrated significant improvements in progression-free survival and objective response rates in patients with RR-DTC and MTC...Despite significant progress, management of advanced thyroid cancer remains challenged by drug resistance and toxicity, underscoring the need for ongoing research and innovation. Furthermore, vast improvements are still required to ensure universal access to molecular testing and targeted therapies.

This study demonstrated superior PRT for selpercatinib compared with control in patients with RET-mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced RET-mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials.

These include immune checkpoint inhibitors (nivolumab, tislelizumab, sintilimab, avelumab), multi-tyrosine kinase inhibitors (cabozantinib, erlotinib, lenvatinib, axitinib, vandetanib), and PARP inhibitors (talazoparib). The most promising combinations are nivolumab/cabozantinib (N = 5, objective response rate (ORR): 100%), lenvatinib/tislelizumab (N = 14, ORR: 93.3%), bevacizumab/erlotinib (N = 43, ORR: 72%), and sintilimab/axitinib (N = 19, ORR: 63.1%). In this review, we will provide a detailed overview of ongoing clinical trials, highlighting the roles of metabolic and epigenetic reprogramming, as well as pro- oncogenic signaling, which together form the backbone for emerging novel targeted treatment strategies. Targeting these specific signaling pathways will shift the therapeutic landscape toward personalized medicine in metastatic FHdRCC.