Caprelsa (vandetanib)

Resistance to RET inhibitors can be acquired through RET copy-number gain and secondary mutations as well as NF1 loss-mediated MAPK pathway activation. This mechanism of resistance can be overcome with dual inhibition of RET and downstream RAS/MAPK signaling, demonstrating clinical potential in RET-mutant MTC.

We present and characterise a novel model derived from CTCs for understanding the plasticity and behaviour of CTCs and advanced breast cancer. CDX_IBP_01 was established from the CTC-enriched fraction obtained from the patient with progressing breast cancer. Once stably re-transplanted and growing in vivo, the transcriptomes of CDX and archived primary BCa1 samples were compared. 2D and 3D in vitro cell cultures were established from sorted human cancer cells from an in vivo xenograft. Phenotypes of established models and their stability were characterised using spectral flow cytometry. The metastatic potential of CDX was evaluated in an in vivo assay. Finally, the applicability of the established model for in vivo and in vitro drug screening was evaluated. Created in https://BioRender.com .

Several multikinase blockers targeting RET have been approved by the FDA for the treatment of cancer: (i) vandetanib for medullary thyroid carcinoma and (ii) cabozantinib, lenvatinib, and sorafenib for differentiated thyroid cancer. Pralsetinib is a specific RET blocker that is FDA-approved for the treatment of medullary thyroid cancer, RET-fusion positive thyroid cancer and NSCLC. Selpercatinib is FDA-approved for the management of RET-mutant medullary thyroid cancer, RET-fusion-positive thyroid cancer, and other RET-fusion-positive solid tumors...Currently, the number of new cases of thyroid cancer bearing RET mutations or RET-fusion proteins is about 13,000 per year and the number of cases of RET-driven NSCLC range from about 2000-4000 per year in the United States. Inactivating RET mutations result in Hirschsprung disease, a congenital disorder leading to aganglionosis of the gastrointestinal tract.

Additionally, the high-risk group showed higher sensitivity to four drugs, with CD14 expression negatively correlated with sensitivity to vandetanib and cabozantinib. This study developed a model based on efferocytosis-associated characteristics to predict the prognosis of HCC patients and those undergoing TACE treatment, thereby facilitating the formulation of personalized treatment plans.

Early multi-kinase inhibitors such as vandetanib and cabozantinib demonstrated modest efficacy with significant toxicity, whereas the selective RET inhibitors selpercatinib and pralsetinib have achieved improved response rates and tolerability...Nonetheless, resistance, driven by secondary mutations and bypass signaling, presents a major therapeutic challenge. Ongoing development of next-generation inhibitors and combination strategies aims to overcome resistance and improve patient outcomes.

Despite vandetanib treatment, the disease progressed and the patient expired. This case highlights a rare presentation of a metastatic neoplasm highly suggestive of RET wild-type MTC with peritoneal involvement, despite the absence of an identifiable primary lesion.

Indeed, the frequency and presentation of these CV toxicities vary according to the TT: arterial hypertension with VEGFR inhibitors, thromboembolic events with abemaciclib, left ventricular dysfunction with osimertinib or BRAF/MEK inhibitors, QTc prolongation with ribociclib or vandetanib, and metabolic disorders (dyslipidemia, hyperglycemia) with PI3K/AKT/mTOR pathway inhibitors. A multidisciplinary approach involving oncologists, cardiologists, primary care physicians, and patients is key. Patient education, optimization of risk factors, and individualized monitoring are the cornerstones of optimal care.

P3, N=291, Active, not recruiting, Loxo Oncology, Inc. | Trial completion date: Feb 2026 --> Nov 2027

In a sciatic nerve ligation model, GelMAMAVP MPs system demonstrated markedly superior analgesic efficacy over the conventional VEGFR2 inhibitor vandetanib...Furthermore, GelMAMAVP MPs distributed in the peripheral nerve stumps indirectly downregulated pain-related proteins (TRPA1/CGRP) in dorsal root ganglia and suppressed spinal microglial activation. Overall, this study presents a comprehensive and safe vascular-targeted strategy promoting nerve end interface self-resolution and prevention of neuropathic pain.

Selpercatinib conferred significant PFS benefit over SoC in treatment-naïve (1L) patients with RET-mutation-positive MTC, with inconclusive results in the ≥2L setting. Matching retrospective real-world data to prospective trial data is feasible. EC arms to single-arm trials may provide evidence supporting the evaluation of comparative effectiveness.

Our findings uncover a novel mechanism underlying TKI-induced cardiotoxicity, involving calpain-dependent degradation of cardiac myofilament proteins and independent of calcium dysregulation. This study highlights the critical role of sarcomere stability in maintaining cardiac function during TKI therapy and identifies calpain as a promising therapeutic target for cardioprotection, with calpain activation rather than calcium dysregulation being the key driver of vandetanib-induced cardiac dysfunction.

By preserving lysosomal function and calcium homeostasis, this strategy addresses a critical unmet need in precision oncology, enabling prolonged, safer use of vandetanib and related tyrosine kinase inhibitors. The discovery of shared lysosomal injury mechanisms across organs also opens avenues for preventing multi-organ toxicities in broader cancer therapies.