Nantong University Affiliated Hospital Licenses Novel Ferroptosis-Targeting Gastric Cancer Drug Patent for RMB 50,000

Recently, the Affiliated Hospital of Nantong University released a public notice on the transformation of scientific and technological achievements, proposing to transfer“Application of CTC-497E21.4 as a Ferroptosis Regulatory Target in the Preparation of Targeted Drugs for Gastric Cancer”The relevant patent portfolio has been licensed to Snibe Co., Ltd. for use, with a licensing fee of50,000 yuan. The inventors of this patent are Associate Professor Jing Rongrong and her team.

The assignee of this patent isSnibe Co., Ltd., is a company focused on the research and development, production, sales, and service of in vitro diagnostic (IVD) products. With chemiluminescence immunoassay technology as its core, it provides end-to-end services covering “instruments + reagents + solutions.” Its product portfolio spans multiple fields, including infectious disease testing, tumor marker detection, endocrine testing, and autoimmune disease testing, catering to scenarios such as hospital clinical laboratories at all levels and third-party independent clinical laboratories.

The present invention discloses the application of CTC-497E21.4 as a ferroptosis regulation target in the preparation of targeted drugs for gastric cancer, belonging to the field of biomedical technology. Based on experimental results, it is inferred that CTC-497E21.4 is associated with ferroptosis in gastric cancer cells and exerts an inhibitory effect on ferroptosis in these cells. This invention elucidates the mechanism by which CTC-497E21.4 regulates ferroptosis in gastric cancer cells, thereby providing a new therapeutic target and technical support for the targeted treatment of gastric cancer.

As one of the most prevalent malignant tumors worldwide, gastric cancer has long faced challenges in its treatment"The Triple Challenge of Scarce Therapeutic Targets, Frequent Emergence of Drug Resistance, and Suboptimal Treatment Efficacy", severely limiting patients' survival prognosis. Clinical data indicate that the 5-year survival rate for patients with advanced gastric cancer is less than 15%, with approximately 60% of patients being insensitive to existing chemotherapy drugs. Moreover, approved targeted therapies are limited to a few targets such as HER2 and Claudin 18.2, leaving a large number of patients without identifiable therapeutic targets in a dilemma of having no available treatment options.

In terms of therapeutic mechanism,, most existing targeted drugs for gastric cancer focus on classic pathways such as cell proliferation and angiogenesis. However, the potent “anti-apoptotic” capacity of tumor cells often leads to drug resistance, which has become a core driver of disease recurrence and progression.

In recent years, ferroptosis, as a novel form of cell death, has opened up new avenues for cancer therapy. By inducing the accumulation of lipid peroxides within tumor cells, thereby compromising the integrity of the cell membrane, it can effectively overcome apoptosis-resistant tumors.

However, current research on ferroptosis-regulating molecules exhibits significant deficiencies. The known regulatory targets (such as SLC7A11 and TFRC) are limited in variety, and the understanding of their mechanisms of action remains insufficiently deep. This has led to slow progress in the development of targeted therapies, making it difficult to meet the diverse clinical treatment needs.

In Target Discovery and DevelopmentLong non-coding RNAs (lncRNAs) have emerged as promising novel therapeutic targets due to their critical regulatory roles in tumorigenesis and tumor progression; however, their translational applications remain significantly lagging. Although CTC-497E21.4 has been validated as a biomarker for gastric cancer detection, its specific functions within tumor cells have long remained unclear. In particular, no prior studies have reported whether it participates in the regulation of ferroptosis or serves as a viable therapeutic target. This knowledge gap has led to the oversight of its potential therapeutic value and has hindered breakthroughs in identifying new effective targets for ferroptosis-targeted therapy in gastric cancer.

Furthermore,Existing ferroptosis-related targeted drugs still suffer from “insufficient specificity and significant side effects.”Since the ferroptosis pathway also performs essential basal functions in normal cells, non-specific activation of ferroptosis can readily cause damage to normal tissues such as the liver and kidneys, thereby limiting the clinical application of related drugs. The current lack of precisely regulated targets further exacerbates this challenge: the inability to achieve precise targeting “exclusively against tumor cells” makes it difficult to balance efficacy and safety, seriously hindering the clinical translation of ferroptosis-targeted therapies.

The core advantage of the patented technology “Application of CTC-497E21.4 as a Ferroptosis Regulatory Target in the Preparation of Targeted Drugs for Gastric Cancer” lies inConstruct a comprehensive solution centered on “novel target discovery + elucidation of regulatory mechanisms,”Achieving breakthroughs across the entire chain—from target discovery and mechanistic elucidation to translational application—thereby fundamentally overcoming the limitations of traditional ferroptosis-based therapies for gastric cancer, which are characterized by single targets and unclear mechanisms of action.

This technology has pioneered a disruptive breakthrough in target innovation—This study overcomes the limitation of the narrow range of existing ferroptosis regulatory targets (such as SLC7A11 and GPX4) and, for the first time, confirms that the long non-coding RNA CTC-497E21.4 is a key regulatory target of ferroptosis in gastric cancer cells.

Previous studies have only identified CTC-497E21.4 as a biomarker for gastric cancer detection, whereas this patent validates its core function through multidimensional experiments. Knockdown of CTC-497E21.4 expression in gastric cancer cells (including MKN-45 and SGC-7901 cell lines) resulted in typical morphological changes associated with ferroptosis (mitochondrial shrinkage and increased membrane density), significantly reduced cell viability, elevated levels of the lipid peroxidation product malondialdehyde (MDA), and accumulation of reactive oxygen species (ROS). Conversely, overexpression of CTC-497E21.4 significantly enhanced cell viability and reduced MDA and ROS levels, demonstrating a reversal effect on ferroptosis-related phenotypes.

This finding fills the research gap regarding the role of CTC-497E21.4 in the regulation of tumor ferroptosis, providing a novel therapeutic target for targeted treatment of gastric cancer.

In terms of mechanism elucidation,This technology elucidates that CTC-497E21.4 influences the ferroptosis process by regulating the expression of SLC7A11 and GPX4, thereby overcoming the challenges of “unclear mechanisms of action and insufficient specificity” associated with traditional ferroptosis-targeted therapies.

First, screening and validation via qRT-PCR and Western blot assays revealed that CTC-497E21.4 specifically regulates the expression of SLC7A11 and GPX4, key molecules in ferroptosis.Following interference with CTC-497E21.4, the expression levels of SLC7A11 and GPX4 were significantly reduced, thereby inhibiting glutathione (GSH) biosynthesis, attenuating the antioxidant activity of GPX4, and ultimately promoting ferroptosis in gastric cancer cells.

Second, functional rescue experiments confirmed that SLC7A11 is a key downstream target molecule of CTC-497E21.4.Overexpression of SLC7A11 effectively reversed the effects induced by CTC-497E21.4 interference, restoring gastric cancer cell viability and reducing MDA and ROS levels, thereby confirming the specificity of this regulatory relationship.

Furthermore, this technology boasts significant advantages in translational application, characterized by “multiple implementation pathways and high adaptability.”Regarding intervention strategies, the patent provides two core implementation pathways: first, direct inhibition of target expression using the CTC-497E21.4 interference plasmid (containing specific shRNA); second, downregulation of its expression through nucleic acid therapeutics such as antisense oligonucleotides and siRNA. Both approaches efficiently promote ferroptosis in gastric cancer cells, offering diversified options for drug development.

Drugs developed based on this target are expected to be compatible with multiple routes of administration, covering commonly used clinical forms such as oral and injectable formulations, thereby meeting the needs of diverse patient populations.

Meanwhile, the targets and pathways involved in this technology have been validated across multiple gastric cancer cell lines, demonstrating broad applicability and laying a solid foundation for subsequent large-scale clinical translation.

Currently, addressing clinical challenges such as chemotherapy resistance and the scarcity of targeted therapeutic options in gastric cancer, ferroptosis, as a novel mechanism of cell death, has become a core focus for R&D teams and corporate strategic planning. Diverse technologies are building multifaceted R&D pipelines centered on “target discovery, drug combinations, and efficacy prediction,” driving the evolution of gastric cancer treatment toward greater precision and efficiency.

Jointly developed by Fudan University Shanghai Cancer Center and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine“Application of SOX13 as a Chemotherapy Biomarker for Gastric Cancer” Technology, providing an innovative solution for predicting ferroptosis resistance and chemotherapy efficacy in gastric cancer.

This study provides the first evidence that SOX13 is highly expressed in ferroptosis-resistant gastric cancer cells. Knockdown of SOX13 significantly enhances the sensitivity of gastric cancer cells to ferroptosis inducers (such as erastin and RSL3) and the chemotherapeutic agent cisplatin, without affecting apoptosis or cell cycle progression.

The co-developed detection kit can specifically quantify SOX13 expression levels using PCR primers, thereby accurately assessing the sensitivity of patients with stage IIIA–C gastric cancer to postoperative cisplatin-based adjuvant chemotherapy and preoperative neoadjuvant chemotherapy. The related achievements have been granted an invention patent and are currently in the clinical translation phase, providing a critical basis for formulating individualized treatment regimens.

Shenzhen Liyunde Biotechnology Co., Ltd.Launched“Imperatorin + Millettia kentingensis flavonoid” anti-gastric cancer drug composition, innovatively employing a combination strategy of natural compounds to induce ferroptosis in gastric cancer cells. This composition combines the two components at a mass ratio of (15–25):1, achieving efficient inhibition of gastric cancer cells by elevating intracellular levels of ROS, MDA, and ferrous ions, while downregulating the expression of ferroptosis-related proteins such as GPX4 and SLC7A11.

In vitro and in vivo experiments have demonstrated that the combination therapy significantly outperforms monotherapy in inhibiting MGC-803 cells, with no evident toxicity to major organs in mice. Currently, this pharmaceutical composition has been granted an invention patent and is in the final stages of preclinical research. It is planned to be developed into various dosage forms, including oral and injectable formulations, to meet the needs of diverse clinical scenarios.

Shandong Second Medical UniversityR&D“Application of LINC02266 and Its Small Interfering RNA” Technology, focusing on long non-coding RNA targets, has opened up new avenues for ferroptosis-based therapy in gastric cancer.

This technology revealed that LINC02266 is highly expressed in gastric cancer tissues and cell lines. Small interfering RNAs (siRNAs), comprising six specific sequences, can significantly increase lipid peroxidation (MDA) levels and decrease glutathione (GSH) levels in BGC-823 gastric cancer cells by inhibiting LINC02266 expression, thereby promoting ferroptosis while suppressing tumor cell proliferation, invasion, and migration.

Relevant achievements have been granted invention patents. The supporting drug composition can be administered via oral or intravenous routes and is currently in the preclinical efficacy validation phase, holding promise as a novel therapeutic option for diffuse infiltrative gastric cancer and other subtypes.