In intermediate-to-advanced HCC, the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS, OS, and ORR.

We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients.

These cases highlight the potential efficacy of selpercatinib in treating intracranial metastases in RET fusion-positive patients with NSCLC after pralsetinib-refractory progression. The key takeaway is that selpercatinib may offer a viable treatment option in such scenarios, although more extensive studies are needed to determine its role as a monotherapy or in combination with other treatments.

P2, N=33, Recruiting, The First Affiliated Hospital with Nanjing Medical University | Initiation date: Mar 2024 --> Dec 2023

The ORR of intrahepatic lesions by CRAFITY 0, 1 and 2 were 37.9%, 35%, 30.6% (p= .688). CRAFITY score is a good predictor of prognosis in HCC patients receiving Len-P.

P2, N=408, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2027 --> Dec 2025

Based on these findings, the patient was diagnosed with stage IIIC2 endometrial cancer (pT1bN2M0, clear cell carcinoma) and received postoperative adjuvant therapy with paclitaxel and carboplatin. Five cycles of pembrolizumab and lenvatinib followed by four cycles of doxorubicin and cisplatin were ineffective. The patient died 13 months after the diagnosis of recurrence.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

Collectively, GFPT2 is potentially useful as a biomarker for prognostic prediction and immune infiltration in a variety of malignancies ,and could lead to exciting new approaches to personalized oncotherapy.

Transcriptomic analysis of these resistant organoids identified key pathways related to KRAS signaling, inflammation, and epithelial-mesenchymal transition (EMT), revealing potential targets for overcoming Lenvatinib resistance. This study provides valuable insights into MASH-related HCC progression and drug resistance, offering a model for further therapeutic research.

P2, N=43, Active, not recruiting, National Cancer Center Hospital East | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2025 --> Aug 2026

P2, N=603, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Our findings suggest lenvatinib is a valuable treatment option for patients with HCC recurrence after LT.

P1/2, N=856, Active, not recruiting, Loxo Oncology, Inc. | Recruiting --> Active, not recruiting

P2, N=13, Recruiting, Children's Hospital of Philadelphia | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Jul 2024

P3, N=328, Not yet recruiting, Affiliated Hospital of Guangdong Medical University; Affiliated Hospital of Guangdong Medical University

P2, N=46, Not yet recruiting, Cancer Hospital, Chinese Academy of Medical Sciences; Cancer Hospital, Chinese Academy of Medical Sciences

P2, N=38, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital); The First Affiliated Hospital of Nanjing Medical University

P2, N=68, Not yet recruiting, Harbin Medical University Cancer Hospital; Harbin Medical University Cancer Hospital

P2, N=36, Recruiting, The First Affiliated Hospital of Dalian Medical University; The First Affiliated Hospital of Dalian Medical University | Not yet recruiting --> Recruiting

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

The development of multi-kinase inhibitors cabonzantinib and vandetanib, and RET-targeted inhibitors selpercatinib, has completely changed the therapeutic arsenal for advanced disease, but their prescription is reserved to progressive disease with high tumor volume or to symptomatic disease inaccessible to local treatment in expert centers from the ENDOCAN-TUTHYREF network. Active surveillance is the alternative of choice for slowly progressing disease.

Activation of Nrf2 signaling by LR HCC cell-derived exosomal miR-301a-3p skewed the transformation of macrophages to the M2 phenotype. Our study provides new findings on the role of miR-301a-3p, suggesting it is a promising therapeutic target to improve HCC lenvatinib resistance.

The combination regimen demonstrated promising efficacy in treating unresectable HCC, accompanied by manageable safety profiles. Furthermore, the results of this investigation suggest that AFP holds promise as predictive biomarkers for this treatment strategy.

P2, N=38, Not yet recruiting, National Cancer Center, Japan

P2, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial primary completion date: Aug 2024 --> Dec 2024

P2, N=39, Completed, Nanfang Hospital, Southern Medical University | Recruiting --> Completed

P2, N=58, Active, not recruiting, The Netherlands Cancer Institute | Trial completion date: Mar 2025 --> Mar 2026

This study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

BAIAP2L2 inhibits the levels of reactive oxygen species (ROS) by regulating GABPB1, thereby promoting cancer properties in HCC and reducing the sensitivity of HCC to lenvatinib. In summary, this study elucidates the role and underlying mechanism of BAIAP2L2 in HCC, providing a potential biomarker and therapeutic target for this disease.

The YAP-HER3 axis is crucial for the survival and adaptive resistance of high YAP-expressing RET-aberrant cancer cells treated with RET-TKIs. Combining YAP/HER3 inhibition with RET-TKIs represents a highly potent strategy for initial treatment.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

STM2457 treatment attenuated the serine synthesis pathway, induced oxidative stress, and sensitized HCC cells to sorafenib and lenvatinib treatments. In conclusion, our findings suggest that targeting m6A could be a potential therapeutic strategy for HCC treatment.

P3, N=1069, Active, not recruiting, Eisai Inc. | Trial completion date: Jul 2024 --> Mar 2026

P2, N=35, Not yet recruiting, University of Chicago

Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes.

To date, this patient continues to show a near complete response to this treatment regimen. To our knowledge, this is the first documented case of SMARCB1-deficient RMC without hemoglobinopathy to receive this treatment regimen and show such a response.

BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.

If, following downstaging, the patient qualifies for liver resection based on locally prevalent resectability criteria, then such therapy is labelled as conversion (from unresectable to resectable) therapy. In unresectable patients treated by a combination of treatment options, serological markers like neutrophil-to-lymphocyte ratio and alpha-fetoprotein are reported to predict treatment responses, thus enabling personalized medicine.

PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA, promoting conversion therapy and improving the prognosis.

Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.