该研究采用两阶段设计，共拟入组约120例受试者，主要研究终点为中枢神经系统客观缓解率(CNS - ORR)。由MD安德森癌症中心(MD Anderson Cancer Center)、约翰‧霍普金斯癌症中心(John Hopkins Sidney Kimmel Comprehensive Cancer Center) 、希望之城癌症中心(City ofHope-Duarte)、西北大学癌症 中心(Robert H. Lurie Comprehensive Cancer Center of NorthwesternUniversity) 、 科罗拉多大学医院 (University of Colorado Hospital) 、 奥古斯塔大学 (AugustaUniversity)、加利福尼亚大学洛杉矶分校 (University of California Los Angeles)等全美近20家头部研究中心共同参与。 格隆汇12月17日丨华昊中天医药-B(02563.HK)宣布，公司全资美国子公司Biostar Pharma,Inc.(「US - Biostar」)已完成其一项重要海外临床研究的首例患者给药： ...

Core Viewpoint - Ferroptosis has emerged as a promising anti-tumor treatment strategy, distinct from apoptosis and necroptosis, characterized by uncontrolled lipid peroxidation and high levels of ferrous ions (Fe2+) and reactive oxygen species (ROS) [2][3][7]. Group 1: Mechanism and Inducers of Ferroptosis - GPX4 utilizes glutathione (GSH) to reduce lipid peroxides to lipid alcohols, making targeting GPX4 or GSH a potential strategy for cancer therapy [3]. - Lipid peroxidation may serve as a "find me" signal, enhancing tumor immunotherapy effectiveness [3]. - Inducers of ferroptosis, such as RSL3 and erastin, have shown efficacy in inducing ferroptosis in mouse tumor models and human tumor cell lines [3][4]. Group 2: Research Findings on Acevaltrate - A recent study identified acevaltrate (ACE) as a novel ferroptosis inducer that targets both PCBP1/2 and GPX4 in colorectal cancer cells, leading to rapid and strong induction of ferroptosis [4][8]. - ACE increases intracellular Fe2+ levels by targeting and reducing the expression of iron chaperone proteins PCBP1/2, while also inhibiting GPX4 activity, disrupting the antioxidant system in colorectal cancer cells [9][12]. - Animal experiments indicate that ACE demonstrates superior therapeutic effects compared to known ferroptosis inducers and first-line clinical cancer drugs like capecitabine and TAS-102 [10][12]. Group 3: Implications for Clinical Treatment - The dual mechanism of ACE not only enhances the induction of ferroptosis but also addresses the compensatory resistance issues associated with single-target ferroptosis inducers [12]. - ACE's multi-target characteristics suggest a potential for high efficacy and low toxicity in selectively killing tumor cells, providing a new strategy for clinical treatment of colorectal cancer [12].

Core Viewpoint - The article narrates the journey of a family dealing with a cancer diagnosis, highlighting the emotional and medical challenges faced by the family as they seek treatment options for the mother diagnosed with duodenal adenocarcinoma and multiple liver metastases. Group 1: Diagnosis and Initial Findings - The mother, previously healthy, was diagnosed with duodenal adenocarcinoma with multiple liver metastases after a routine health check-up revealed a 4.7 cm lesion on the liver [4][5][8] - Initial assessments indicated no surgical options available due to the extent of the disease [4][10] Group 2: Diagnostic Journey - The family sought further evaluations, leading to a series of tests including ultrasound and MRI, which confirmed the presence of malignant lesions [6][8][20] - Tumor markers showed elevated CA199 levels at 736, indicating a poor prognosis [7][8] Group 3: Treatment Options and Decisions - The family explored treatment options, including participation in clinical trials for chemotherapy and targeted therapy [14][27] - The mother expressed a desire for a PET CT scan to assess the extent of metastasis, which revealed a primary tumor in the duodenum with liver metastases [17][19] Group 4: Pathological Confirmation - Biopsy results confirmed the diagnosis of duodenal cancer with liver metastases, leading to a revised treatment plan [22][25] Group 5: Treatment Strategy - The treatment plan included a combination of chemotherapy and targeted therapy, with the potential for surgery if the tumor responded well [27][28] - The family joined a support group that provided valuable information and emotional support during the treatment process [28][29] Group 6: Surgical Considerations - After successful chemotherapy, the mother was evaluated for surgical options, with a focus on minimizing risks associated with the complex surgery [39][56] - The surgical team emphasized the importance of thorough imaging to guide the surgical approach, leading to a decision to proceed with surgery [49][50] Group 7: Surgical Outcome - The surgery was successful, with the removal of both the primary tumor and liver metastases, and pathology indicated no active disease in the liver [59][60] - Post-operative recovery was complicated by fever and other issues, but the medical team remained optimistic about the mother's recovery [67][70]