Discovery of a selective dual-specificity tyrosine phosphorylation-regulated kinase 1B inhibitor with anti-adipogenic and anti-diabetic activities.

Background: Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) is implicated in metabolic diseases, with high expression linked to adipocyte differentiation and metabolic disorders. This study investigated the anti-adipogenic and anti-diabetic effects of a novel selective DYRK1B inhibitor, N-(4-(3-(4-methoxyphenyl)-1H-pyrazolo [3,4-b]pyridin-5-yl) phenyl)acetamide (KS-40070).

Methods: The efficacy of KS-40070 was evaluated using 3T3-L1 cells, adipose-derived mesenchymal stem cells (ADMSC), and diet-induced obesity (DIO) mice.

Nemvaleukin alfa monotherapy in patients with advanced melanoma and renal cell carcinoma: results from the phase 1/2 non-randomized ARTISTRY-1 trial.

Background: Despite improved outcomes with immune checkpoint inhibitors (ICIs) and their combinations in advanced solid tumors, a subset of patients remains unresponsive or progresses, highlighting an unmet need for novel treatments with durable benefit. Nemvaleukin alfa (nemvaleukin, ALKS 4230) demonstrated manageable safety and antitumor activity, alone and in combination with pembrolizumab, across heavily pretreated advanced solid tumors in the ARTISTRY-1 study. We report in-depth antitumor activity, safety, pharmacokinetics, and pharmacodynamics of nemvaleukin monotherapy at the recommended phase 2 dose (RP2D) in advanced melanoma and renal cell carcinoma (RCC) cohorts from ARTISTRY-1.

Targeting iron regulatory protein 2 (IRP2) to disrupt iron metabolism enhances radiosensitivity through mitochondrial dysfunction in breast cancer cells.

Iron regulatory protein (IRP2) plays a key role in regulating iron metabolism and enables cell survival by activating mitochondrial function. Targeting IRP2 to disrupt iron homeostasis is a promising strategy for enhancing the efficacy of cancer treatments. Depletion of IRP2 in breast cancer (BC) cells is associated with sensitivity to radiation therapy (RT), and inhibition of IRP2 prior to RT significantly reduces cell viability compared with radiation treatment alone.

Efficacy and Safety of Ifosfamide and Mesna in Metastatic Castration-Resistant Prostate Cancer after Taxane-Based Chemotherapy and Novel Hormonal Therapy Failure.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789).

Materials And Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1-3, repeated every 21 days.

Number of Lymph Nodes Examined as a Prognosis Factor in Patients With Stage II or III Colon Cancer.

Background: Lymph node (LN) examination is important for staging colorectal cancer. Examining < 12 LN has been associated with a poor prognosis. However, surgical and pathological advances have led to increase examined LN, necessitating the reassessment of the best cutoff for prognosis.

Continuous multimodal data supply chain and expandable clinical decision support for oncology.

The study introduces a clinical decision support system (CDSS) developed at a single academic cancer center, integrating real-time clinical, genomic, and imaging data for over 170,000 patients across 11 cancer types. We have developed the Yonsei Cancer Data Library (YCDL) data integration framework to continuously collect and update multimodal datasets comprising over 800 features per case. Quality control measures, using 143 logical comparisons, addressed missing data and outliers, achieving median accuracies of 92.

A Multicenter Phase II Study of Modified FOLFIRINOX for First-line Treatment for Advanced Urachal Cancer (ULTMA; KCSG GU20-03).

Purpose: To assess the efficacy and safety of the first-line modified FOLFIRINOX in patients with advanced urachal cancer.

Materials And Methods: The ULTIMA trial (NCT04611724) is a single-arm, open-label, multicenter phase II study evaluating modified FOLFIRINOX (Oxaliplatin 85 mg/m2 over 2 hours, Irinotecan 150 mg/m2 over 1.5 hours, Leucovorin 400 mg/m2 over 2 hours, and 5-FU 2400 mg/m2 over 46 hours) plus prophylactic pegteograstim in patients with recurrent or metastatic urachal cancer every 2 weeks for up to 12 cycles, or until disease progression or unacceptable toxicity.

Efficacy and safety of pembrolizumab in patients with advanced urothelial carcinoma deemed potentially ineligible for platinum-containing chemotherapy: Post hoc analysis of KEYNOTE-052 and LEAP-011.

Background: First-line pembrolizumab monotherapy is a standard of care for platinum-ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists. This study aimed to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with UC who met various criteria for platinum ineligibility.

FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin-RAD51 Downregulation.

: Irinotecan, a camptothecin (CPT) derivative, is commonly used as a first-line therapy for colorectal cancer (CRC), but resistance remains a significant challenge. This study aims to explore the therapeutic potential of FL118, another CPT derivative, with a focus on overcoming resistance to irinotecan. The effects of FL118 on CRC cells were evaluated, and bioinformatics analysis was performed on RNA-seq data.

Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.

Background: Dysregulation of iron metabolism is implicated in malignant transformation, cancer progression, and therapeutic resistance. Here, we demonstrate that iron regulatory protein 2 (IRP2) preferentially regulates iron metabolism and promotes tumor growth in colorectal cancer (CRC).

Methods: IRP2 knockdown and knockout cells were generated using RNA interference and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 methodologies, respectively.

Real-world incidences and risk factors of immune-related adverse events in patients treated with immune checkpoint inhibitors: A nationwide retrospective cohort study.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are rare but fatal, requiring systemic steroid use. Therefore, to examine the outcomes, incidence, timing, and risk factors of ICI-associated steroid-requiring severe irAEs, we conducted a nationwide, retrospective, cohort study utilizing the Korean Health Insurance and Review Assessment database. We identified 357,010 patients with lung cancer, bladder cancer, or skin melanoma, eligible for ICI reimbursement in Korea between January 2012 to June 2020.

Nuclear Localization of Yes-Associated Protein Is Associated With Tumor Progression in Cutaneous Melanoma.

Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry.

Phase II study of nivolumab in patients with genetic alterations in DNA damage repair and response who progressed after standard treatment for metastatic solid cancers (KM-06).

Background: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies.

Exploring Molecular Genetic Alterations and RAF Fusions in Melanoma: A Belvarafenib Expanded Access Program in Patients with RAS/RAF-Mutant Melanoma.

Background: Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP).

Patients And Methods: Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023.

Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.

Background: No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma.

Methods: We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.

Synthetic Data Improve Survival Status Prediction Models in Early-Onset Colorectal Cancer.

Purpose: In artificial intelligence-based modeling, working with a limited number of patient groups is challenging. This retrospective study aimed to evaluate whether applying synthetic data generation methods to the clinical data of small patient groups can enhance the performance of prediction models.

Materials And Methods: A data set collected by the Cancer Registry Library Project from the Yonsei Cancer Center (YCC), Severance Hospital, between January 2008 and October 2020 was reviewed.

Treatment Patterns and Prognosis of Palliative Chemotherapy Combined With Targeting Agents in Patients With Unresectable Metastatic Colorectal Cancer: CHOICE, A Multicenter Longitudinal Observational Study.

Background/aim: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents.

Patients And Methods: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors.

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial.

Background: Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).

Objective: To evaluate pembrolizumab plus either lenvatinib or placebo as first-line therapy for advanced UC in the phase 3 LEAP-011 study.

Design, Setting, And Participants: Patients with advanced UC who were ineligible for cisplatin-based therapy or any platinum-based chemotherapy were enrolled.

Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.

Purpose: To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).

Methods: SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors.

A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13).

Background: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT.

Objective: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations.