sunitinib

A paired Bayesian strategy, graded priors for efficacy and no-borrowing priors for safety, produced transparent posterior probability summaries for the Japanese subgroup. This framework illustrates how borrowing can narrow uncertainty when exchangeability is plausible, while clarifying toxicity domains that may warrant closer monitoring, using published trial data.

In summary, ZC3H13-mediated m6A modification stabilizes sFRP-4 expression, which suppresses Wnt/β-catenin signaling and attenuates the sunitinib resistance of RCC. The ZC3H13/sFRP-4 axis may represent a promising therapeutic target in RCC.

Importantly, combination treatment with olaparib and sunitinib showed superior antitumor efficacy in ccRCC PDOs. This study demonstrates that PARP9 promotes sunitinib resistance in ccRCC by activating the STAT1/IRF1 pathway and upregulating ISG15/IFIT1.

P2, N=35, Recruiting, Bai-Rong Xia

Lisaftoclax, a small-molecule inhibitor that disrupts the DHODH-TRIM28 interaction, potentiates sunitinib efficacy and exerts a synergistic therapeutic effect. Collectively, our findings identify DHODH as a critical therapeutic target for overcoming sunitinib resistance in RCC and provide a novel strategy for the treatment of RCC.

Multi-target agents are no longer constrained by single-target effects; however, issues of balanced potency, ADMET, and control still exist. The combination of AI, quantum computing, and precision polypharmacology may enable more effective multi-target interventions to address unmet demands in complex diseases.

These findings suggest that ALDH1L2 contributes to reduced sunitinib sensitivity in RCC organoids by attenuating ferroptosis-related responses. HA-1 may improve the response of RCC organoids to sunitinib by targeting ALDH1L2, supporting further evaluation of this combination strategy.

P3, N=482, Recruiting, Cogent Biosciences, Inc. | Active, not recruiting --> Recruiting

P1/2, N=156, Completed, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

TCM acts as a multi-target network modulator against RCC. That could help overcome drug resistance and improve current therapies. Future research should focus on chemical standardization, pharmacokinetic profiling, and biomarker-driven clinical trials.

P1, N=41, Recruiting, University of Colorado, Denver | Trial completion date: Feb 2027 --> Aug 2029 | Trial primary completion date: Aug 2026 --> Aug 2027