P2, N=35, Recruiting, University of California, Irvine | Trial primary completion date: Jun 2026 --> Oct 2026

We describe a patient with radioactive iodine-refractory, metastatic oncocytic thyroid carcinoma with an NBN gene (c.2166_2167delGCinsAT) pathogenic variant, who developed progressive disease despite receiving systemic therapy with lenvatinib and pembrolizumab. A mutual exclusivity analysis demonstrated a tendency for pathogenic variants in one MRN complex genes to co-occur with pathogenic variants in the other two MRN complex genes. In conclusion, the MRN complex pathogenic variants could be potentially oncogenic in TCs and may be linked to aggressive forms of TC.

We identified FDA-approved compounds acting through these pathways, three of which, Ribociclib, Ponatinib, and Dasatinib, showed superior efficacy to current therapies across renal cancer cell lines in preclinical screens. By acting through mechanisms distinct from current therapies, they represent promising candidates for combination strategies aimed at overcoming resistance and improving clinical outcomes in ccRCC.

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.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and the available targeted therapies (e.g., sorafenib, lenvatinib) have limited options and frequent drug resistance. These compounds synergize with conventional targeted agents to overcome drug resistance through direct cytotoxicity or targeting hypertrophic lysosomal drug release. This article reviews the regulation of LDCD and the role of natural products in HCC based on PubMed, Web of Science and CNKI databases, aiming to providing a reference for the treatment of drug-resistant liver cancer.

Treatment by CM in combination with SB could decrease neoplastic features in HCC group. The hepatic expression of Bcl2 was decreased, and the release of cytosolic cathepsin B was increased in the combination group. Also, the hepatic concentration of Beclin-1 decreased in the combination group and there was autophagosome accumulation in transmission electron microscope (TEM). The results indicate that the concomitant use of CM and SB may be considered a possible new therapeutic option in managing HCC by targeting the cathepsin B/Bcl2/Beclin-1 pathway.

This specific clone persisted after discontinuation, suggesting a role in the sustained immune surveillance of residual leukemia stem cells. These findings suggest that the quality of immune reconstitution, specifically the induction of innate-like effector T-cell clones, may be a more critical determinant of TFR success than the absolute duration of therapy.

P2, N=30, Completed, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Not yet recruiting --> Completed | Trial completion date: Aug 2024 --> Sep 2025 | Trial primary completion date: Mar 2024 --> Sep 2025

Functional status and symptom control were maintained in most patients during treatment, based on routine clinical assessment. These findings suggest that cabozantinib may represent a clinically meaningful treatment option for selected patients with metastatic chRCC and support its further evaluation in this rare disease subtype.

Furthermore, in PDX model established using AML cells from Gilteritinib-resistant patients, the degrader showed significantly superior therapeutic efficacy compared to the combination treatment of Gilteritinib and Imatinib. As a candidate drug molecule, this degrader exhibits promising potential for clinical translation.

After the first TFR attempt, major molecular response (MMR) was lost, and ponatinib was initiated but discontinued because of cerebral infarction. Imatinib was reintroduced, leading to the reachievement of a deep molecular response. This case underscores the importance of careful patient selection and long-term molecular monitoring following TFR attempts, including those involving novel TKIs such as asciminib.

Targeting the ATX-LPA axis represents a promising strategy to overcome resistance to current TKI-ICI combinations.