Gastrointestinal Stromal Tumor (GIST)

Gastrointestinal stromal tumor (GIST) stands as a formidable challenge within the medical realm, with its genesis rooted in intricate gene mutations that unfurl a convoluted network of pathogenic factors. Our company has professional technology and experience in the diagnosis and therapeutics of rare diseases like GIST, enabling us to decode the complex molecular landscape of GIST, paving the way for a new era of personalized therapeutics.

Introduction to GIST

Gastrointestinal stromal tumor (GIST) is a rare form of tumor that primarily affects the gastrointestinal tract, with incidences globally standing at around 1 in every 100,000 individuals. The most common locations for these tumors are the stomach and small intestine, leading to symptoms such as gastrointestinal obstruction, pain, and bleeding, among others (Fig.1).

Fig.1 The anatomic distribution of GIST. (Li, B., et al., 2023)

The diverse spectrum of mutations observed in GIST individuals gives rise to distinct molecular subtypes, each with unique biological characteristics and implications. These subtypes serve as the foundation for developing individualized therapeutic plans that target the specific genetic alterations driving tumor growth.

Pathogenesis of GIST

In the realm of GIST pathogenesis, the majority of individuals exhibit activated mutations in crucial genes such as c-KIT (CD117) and PDGFRA receptor tyrosine kinases. These mutations drive tumorigenesis and serve as important therapeutic targets. However, a subset of GIST cases, known as wild-type GIST (WT-GIST), present without mutations in KIT and PDGFRA (Fig.2). These tumors may harbor mutations in genes like Succinate dehydrogenase (SDH)-dependent or be associated with neurofibromatosis type 1 (NF1).

Fig.2 The genomic distribution of GIST. (Li, B., et al., 2023)

Diagnostics Development of GIST

Immunohistochemistry (IHC)
Immunohistochemistry (IHC) plays a pivotal role in the diagnostic workup of GISTs, utilizing markers such as CD117, DOG-1, CD34, SMA, SDHB, and Ki-67. Although IHC provides valuable information, the advent of gene sequencing technologies has provided more messages in GISTs.

Next-generation sequencing (NGS)
Next-generation sequencing (NGS) has emerged as a powerful tool in simultaneously analyzing multiple molecular variations, enabling precise identification of specific mutation types of GIST. The application of NGS offers heightened sensitivity compared to traditional Sanger sequencing.

Therapeutics of GIST

Small Molecule Drug Therapy

Therapeutics for GIST typically involve surgery to remove the tumor, followed by targeted therapy using small molecule drugs such as imatinib, sunitinib, or regorafenib to inhibit the growth of the tumor and prevent a recurrence. Advances in targeted therapies have significantly improved outcomes for individuals with GIST, and ongoing research continues to explore new therapeutic options for this disease.

Gene Therapy

Gene therapy aims to introduce genetic material into the tumor cells to target specific genes or pathways involved in tumor growth and survival. Incorporating advanced technologies like CRISPR-Cas9 and small interfering RNA offers a revolutionary approach to target and normalize gene expression abnormalities in GIST.

Immunotherapy

Immunotherapy has shown promise in treating GIST by enhancing the body's immune response against the tumor. The therapeutic antibodies targeting programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and small molecule inhibitors such as IDO inhibitors can alter the immune environment by activating CD8⁺ T cells to exert anticancer functions.

Our Services

Our company has been committed to the development and research of rare disease diagnostic and therapeutic platforms. By leveraging cutting-edge technologies and insights, we aim to revolutionize the management of GIST, ushering in a new era of personalized therapeutics that holds immense promise for enhancing individual care and outcomes.

Platforms of GIST Therapy Development

Animal Models of GIST

The animal models can help researchers understand the molecular mechanisms underlying GIST development and progression, as well as test potential therapeutic strategies. Our company can offer animal models to meet your specific research needs.

Xenograft Models
The xenograft model of GIST involves the implantation of human GIST tumor cells or tissues into immunocompromised mice. This allows researchers to study the growth and behavior of GIST tumors in a controlled laboratory setting.
Optional Models	GIST882 model, UZLX-GIST model
Genetically Engineered Models
Some common mutations in the Kit gene that are associated with GIST include exon 11 mutations (such as deletions, substitutions, or insertions) and exon 9 mutations (such as duplications or deletions). By using techniques such as gene targeting, CRISPR/Cas9 genome editing, or transgenic to build animal models with these specific mutations in the Kit gene.
Optional Models	Kit^V558Δ/+ mouse model
Optional Species	Mice, Rats, Others

With professional expertise and extensive experience in rare disease diagnosis and therapeutics, our company is at the forefront of developing advanced therapeutic solutions for GIST and can provide animal models of GIST, to support your pharmacokinetics study and drug safety evaluation, providing help for more accurate and effective research and therapeutics of this complex disease.

If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

Li, B., et al., "Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers." Molecular cancer 22.1 (2023): 71.
Venkataraman V., George S., and Cote G. M. "Molecular advances in the treatment of advanced gastrointestinal stromal tumor." The oncologist 28.8 (2023) :671-681.
Schaefer, I. M., DeMatteo, R. P., and Serrano, C., "The GIST of advances in treatment of advanced gastrointestinal stromal tumor." American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting 42 (2022): 1–15.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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