Pharmacological targeting of casein kinase 1δ suppresses oncogenic NRAS-driven melanoma.

Activating mutations in NRAS account for 15-20% of melanoma, yet effective anti-NRAS therapies are still lacking. In this study, we unveil the casein kinase 1δ (CK1δ) as an uncharacterized regulator of oncogenic NRAS mutations, specifically Q61R and Q61K, which are the most prevalent NRAS mutations in melanoma. The genetic ablation or pharmacological inhibition of CK1δ markedly destabilizes NRAS mutants and suppresses their oncogenic functions.

Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial.

Neoadjuvant PD-1 inhibitor is promising in cutaneous melanoma but remains unknown in acral melanoma (AM). This phase Ib trial study (Clinicaltrials.gov NCT04197882) assessed the efficacy and safety of the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable AM.

A phase II study of efficacy and safety of the MEK inhibitor tunlametinib in patients with advanced NRAS-mutant melanoma.

Background: NRAS-mutant melanoma is an aggressive subtype with poor prognosis; however, there is no approved targeted therapy to date worldwide.

Methods: We conducted a multicenter, single-arm, phase II, pivotal registrational study that evaluated the efficacy and safety of the MEK inhibitor tunlametinib in patients with unresectable, stage III/IV, NRAS-mutant melanoma (NCT05217303). The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.

SOX10 deficiency-mediated LAMB3 upregulation determines the invasiveness of MAPKi-resistant melanoma.

Melanoma that develops adaptive resistance to MAPK inhibitors (MAPKi) through transcriptional reprograming-mediated phenotype switching is associated with enhanced metastatic potential, yet the underlying mechanism of this improved invasiveness has not been fully elucidated. In this study, we show that MAPKi-resistant melanoma cells are more motile and invasive than the parental cells. We further show that LAMB3, a β subunit of the extracellular matrix protein laminin-332 is upregulated in MAPKi-resistant melanoma cells and that the LAMB3-Integrin α3/α6 signaling mediates the motile and invasive phenotype of resistant cells.

Microwave ablation of the lung: Comparison of 19G with 14G and 16G microwave antennas in porcine lung.

Background: Percutaneous image-guided thermal ablation has an increasing role in the treatment of primary and metastatic lung tumors. Although microwave ablation (MWA) has emerged advantageous as a new ablation technology, more research is needed to improve it. This study aims to investigate the ablation zone of three microwave antennas in ex vivo porcine lung.

First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations.

Background: HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.

Methods: This was a multicenter phase 1 study.

Phase I pharmacokinetic study of an oral, small-molecule MEK inhibitor tunlametinib in patients with advanced NRAS mutant melanoma.

Malignant melanoma is an aggressive disease. Tunlametinib (HL-085) is a potent, selective, and orally bioavailable MEK1/2 inhibitor. The objective of this study was to determine the pharmacokinetics (PK) of tunlametinib and its main metabolite M8 in patients with -mutant melanoma following a single dose and multiple doses in a phase I safety and PK study.

FMRP ligand circZNF609 destabilizes RAC1 mRNA to reduce metastasis in acral melanoma and cutaneous melanoma.

Background: Melanoma is a type of malignant tumor with high aggressiveness and poor prognosis. At present, metastasis of melanoma is still an important cause of death in melanoma patients. However, the potential functions and molecular mechanisms of most circular RNAs (circRNAs) in melanoma metastasis remain unknown.

Surgical Outcomes of Vaginal or Cervical Melanoma.

To evaluate the effectiveness of radical resection compared with non-radical resection for vaginal or cervical melanoma. We retrospectively analysed the clinical data of post-operative patients with primary lower genital tract melanoma hospitalised at Peking University Cancer Hospital between Jan 2014 and Dec 2020. The study endpoints were recurrence-free survival (RFS) and overall survival (OS).

Safety Profile of Immunotherapy Combined With Antiangiogenic Therapy in Patients With Melanoma: Analysis of Three Clinical Studies.

To describe the frequency and spectrum of treatment-related adverse events (TRAEs) of immunotherapy combined with antiangiogenic therapy in patients with melanoma. This retrospective cohort study included three clinical trials on patients with stage III/IV melanoma treated with anti-PD 1 and antiangiogenic therapy. We analyzed data from 72 patients with a median follow-up time of 25.

The combination therapy with the cytotoxic T lymphocyte-associated antigen-4 and programmed death 1 antibody-induced asthma in a patient with advanced melanoma.

The combination of programmed death 1 (PD-1) inhibitors and cytotoxic T lymphocyte-associated antigen-(CTLA-4) inhibitors have markedly improved the survival of melanoma patients. We report the case of a patient with advanced melanoma who developed asthma during anti-PD-1 and anti-CTLA-4 combination therapy. The patient was a 57-year-old woman enrolled in a clinical trial regarding novel CTLA-4 antibody and sintilimab treatment.

The Impact of Liver Metastasis on Anti-PD-1 Monoclonal Antibody Monotherapy in Advanced Melanoma: Analysis of Five Clinical Studies.

Anti-programmed cell death protein 1 (PD-1) monoclonal antibody therapy is becoming a standard treatment for advanced melanoma that produces durable responses and prolonged survival, but the prognosis of patients with liver metastases is still unsatisfactory. Here, we analyzed five clinical studies (second-line or later, JS001-I-PK, CT4, KN151, BGB-A317-102, and SHR-1210-102; performed between 2015 and 2018) of anti-PD-1 monotherapy for advanced melanoma to explore prognostic variables for patients with liver metastases. A total of 168 patients with stage IV melanoma were included, among which 47 had liver metastasis and 121 did not.

Primary malignant melanoma of the esophagus: A retrospective analysis of clinical features, management, and survival of 76 patients.

Background: Primary malignant melanoma of the esophagus (PMME) is rare. Patients with advanced melanoma of esophageal origin tend to have lower response rates to traditional therapies than those with other melanomas. We report our experience of 12 patients with PMME administered PD-1 inhibitors.