FOLR1: A Promising Therapeutic Target for Precision Cancer Therapy
28 Feb 2026
Concept
Folate Receptor 1 (FOLR1), a glycosylphosphatidylinositol (GPI)-anchored transmembrane glycoprotein, is a key mediator of cellular folate uptake and metabolism in human cells. As a high-affinity folate-binding protein, FOLR1 facilitates the internalization of folate and its analogs into cells via receptor-mediated endocytosis, playing an indispensable role in supporting DNA synthesis, repair, and methylation—fundamental processes for cell proliferation and survival. Under physiological conditions, FOLR1 expression is restricted to a subset of normal rapidly proliferating epithelial and embryonic cells. However, FOLR1 exhibits aberrant overexpression in a broad spectrum of epithelial-origin malignancies, including ovarian, endometrial, breast, lung, pancreatic, and brain cancers. This cancer-specific overexpression, coupled with its functional role in sustaining tumor cell growth and progression, makes FOLR1 a highly attractive and clinically relevant target for precision cancer therapy, enabling the development of selective anti-tumor strategies that minimize off-target effects on normal tissues.
Research Frontiers
FOLR1 research is a rapidly evolving frontier in oncology and precision medicine, with cutting-edge studies focused on unraveling its mechanistic role in tumorigenesis and translating this knowledge into novel therapeutic strategies. Key research frontiers include:
- Mechanistic dissection of FOLR1-driven tumor progression: Investigating the non-metabolic signaling functions of FOLR1 in cancer cells, including its crosstalk with oncogenic pathways (e.g., PI3K/Akt, MAPK) to regulate cell proliferation, invasion, and drug resistance—moving beyond its well-characterized role in folate transport.
- Development of next-generation FOLR1-targeted therapeutics: Engineering novel FOLR1-directed agents such as antibody-drug conjugates (ADCs) with optimized payloads, bispecific antibodies, chimeric antigen receptor (CAR) T cells, and folate-drug conjugates with enhanced tumor selectivity and efficacy.
- Identification of FOLR1-based predictive biomarkers: Defining molecular and clinical biomarkers that stratify cancer patients most likely to respond to FOLR1-targeted therapy, including FOLR1 expression levels, folate metabolism pathway activity, and tumor histological subtypes.
- Combination therapy strategies: Exploring rational combinations of FOLR1-targeted therapy with chemotherapy, immunotherapy (e.g., PD-1/PD-L1 inhibitors), anti-angiogenic agents, and metabolic inhibitors to overcome drug resistance and enhance anti-tumor efficacy.
- FOLR1 in cancer metastasis and microenvironment remodeling: Elucidating the role of FOLR1 in tumor cell invasion, metastatic colonization, and the remodeling of the tumor microenvironment (TME), including its impact on cancer-associated fibroblasts and immune cell infiltration.
- Novel FOLR1 imaging agents: Developing high-sensitivity FOLR1-targeted molecular imaging probes (e.g., fluorescent, PET, SPECT) for early cancer diagnosis, tumor staging, and real-time monitoring of therapeutic response.
Research Significance
FOLR1 has emerged as a pivotal target in cancer research and therapy, with profound significance for precision oncology, drug development, and improving patient outcomes:
- Enables cancer-specific targeted therapy: FOLR1’s restricted expression in normal tissues and robust overexpression in a wide range of malignancies creates a unique therapeutic window, allowing the development of agents that selectively eliminate FOLR1-positive tumor cells while sparing healthy tissue—reducing the toxic side effects associated with conventional chemotherapy.
- Addresses unmet clinical needs in hard-to-treat cancers: FOLR1 is highly expressed in ovarian cancer (≥70% of patients), a disease with poor prognosis due to late diagnosis and chemoresistance, as well as other aggressive malignancies such as pancreatic and triple-negative breast cancer. FOLR1-targeted therapy offers a new treatment paradigm for these currently underserved patient populations.
- Serves as a prognostic biomarker for cancer progression: FOLR1 overexpression correlates with poor clinical outcomes (reduced disease-free survival [DFS] and overall survival [OS]) in multiple cancers, including breast, ovarian, and endometrial cancer. It can be used as a prognostic biomarker to stratify patients and guide personalized treatment decisions.
- Drives innovation in anti-cancer drug development: The unique biological properties of FOLR1 have spurred the development of diverse therapeutic modalities, from ADCs and monoclonal antibodies to CAR-T cells and folate-conjugated drugs, expanding the arsenal of precision oncology agents and fostering technological innovation in drug delivery.
- Links metabolic reprogramming to tumorigenesis: FOLR1 is a key node in cancer cell metabolic reprogramming, a hallmark of cancer. Studying FOLR1 provides critical insights into how tumor cells adapt their folate metabolism to support uncontrolled proliferation, uncovering new metabolic vulnerabilities that can be exploited for therapy.
- Facilitates early cancer detection and monitoring: FOLR1-targeted imaging agents enable the early detection of FOLR1-positive tumors and real-time monitoring of therapeutic response, allowing for timely intervention and treatment adjustment—improving the likelihood of successful cancer treatment.
Mechanisms & Research Methods
1. Core Biological Characteristics of FOLR1
FOLR1 is a 38 kDa GPI-anchored glycoprotein encoded by the FOLR1 gene on chromosome 11q13, with distinct structural and functional properties that underpin its role in folate metabolism and cell signaling:
Key Role in Cellular Folate Metabolism
Folate (vitamin B9) is an essential micronutrient required for one-carbon metabolism, which supports DNA synthesis, DNA repair, and epigenetic methylation of DNA and histones—processes critical for cell cycle progression and genome stability. FOLR1 mediates the high-affinity uptake of folate (Kd ≈ 100 pM) from the extracellular environment into cells via receptor-mediated endocytosis: after binding folate or its analogs, the FOLR1-folate complex is internalized into clathrin-coated vesicles, folate is released into the cytoplasm at acidic endosomal pH, and FOLR1 is recycled back to the cell surface. This process ensures a continuous supply of folate to meet the metabolic demands of proliferating cells. Under normal physiological conditions, FOLR1 expression is limited to the choroid plexus, kidney proximal tubules, placenta, and certain epithelial cells, reflecting the folate requirements of these rapidly dividing or specialized tissues.
Structural Architecture of FOLR1
FOLR1 features a modular structure optimized for folate binding and cellular trafficking, consisting of three functional domains:
- Extracellular folate-binding domain: The N-terminal extracellular domain contains the high-affinity folate-binding pocket, which specifically recognizes and binds folic acid and its reduced analogs (e.g., 5-methyltetrahydrofolate). Glycosylation of this domain is critical for maintaining receptor folding, stability, and folate-binding affinity.
- GPI-anchored transmembrane domain: Unlike classic transmembrane receptors with a cytoplasmic tail, FOLR1 is anchored to the cell membrane via a GPI moiety, which mediates its cell surface localization and recycling.
- Signaling-associated motifs: Although FOLR1 lacks an intrinsic cytoplasmic signaling domain, it interacts with membrane-associated signaling molecules (e.g., Src family kinases) to transduce intracellular signals that regulate cell proliferation, survival, and migration—extending its function beyond folate transport to direct oncogenic signaling.
2. FOLR1 Overexpression in Cancer and Correlation with Tumor Progression
FOLR1 is one of the most frequently overexpressed receptors in epithelial malignancies, with its upregulation tightly linked to tumor aggressiveness, metastatic potential, chemoresistance, and poor patient prognosis.
Pan-Cancer Overexpression of FOLR1
FOLR1 exhibits significant overexpression in a diverse range of human cancers, with the highest expression levels observed in ovarian cancer (≥70% of patients), endometrial cancer, and triple-negative breast cancer (TNBC). It is also frequently overexpressed in non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), glioblastoma, and colorectal cancer. This cancer-specific overexpression is driven by multiple mechanisms, including epigenetic dysregulation (hypomethylation of the FOLR1 promoter), transcriptional activation by oncogenic transcription factors (e.g., MYC, STAT3), and increased mRNA stability—all of which converge to enhance FOLR1 expression and support the high folate metabolic demands of tumor cells.
FOLR1 Overexpression and Clinical Prognosis
Clinical and translational studies have established a strong correlation between FOLR1 overexpression and poor prognostic outcomes in multiple cancers, with robust hazard ratio (HR) data validating its role as a prognostic biomarker:
- Breast cancer: High FOLR1 expression is associated with a 2.66-fold increased risk of reduced DFS (HR=2.66) and a 1.97-fold increased risk of reduced OS (HR=1.97), meaning FOLR1-overexpressing patients have a 97% higher risk of cancer-related death.
- Ovarian cancer: In serous ovarian cancer—the most common and aggressive subtype—FOLR1 overexpression correlates with a 2.45-fold higher risk of reduced DFS (HR=2.45) and a 3.60-fold higher risk of reduced OS (HR=3.60). FOLR1 overexpression is also linked to chemoresistance in high-grade, late-stage, and aneuploid ovarian cancers.
- Endometrial cancer: FOLR1 overexpression is associated with a 1.3-fold increased risk of reduced DFS (HR=1.3), highlighting its role in endometrial tumor progression.
- Other cancers: In pancreatic and lung cancer, FOLR1 overexpression correlates with increased tumor invasiveness, metastatic potential, and chemoresistance, even in the absence of a direct link to DFS/OS.
3. Mechanistic Role of FOLR1 in Cancer Pathogenesis
FOLR1 promotes cancer progression through two complementary mechanisms: metabolic support of tumor proliferation and oncogenic signaling modulation, both of which contribute to the malignant phenotype of FOLR1-positive cancer cells:
Metabolic Reprogramming for Uncontrolled Proliferation
Tumor cells exhibit a high rate of proliferation and thus have an increased demand for folate to support DNA synthesis and methylation. FOLR1 overexpression enables cancer cells to efficiently sequester folate from the tumor microenvironment—an environment characterized by low folate availability—giving them a metabolic advantage over normal cells. This enhanced folate uptake sustains one-carbon metabolism, fueling uncontrolled cell cycle progression and genome maintenance in tumor cells.
Oncogenic Signaling and Tumor Malignancy
Beyond its metabolic role, FOLR1 modulates intracellular oncogenic signaling pathways to promote cancer cell proliferation, invasion, migration, and chemoresistance. Through its interaction with membrane-associated signaling molecules (e.g., Src, PI3K), FOLR1 activates downstream pathways such as PI3K/Akt and MAPK/ERK, which regulate cell survival and proliferation. FOLR1 also promotes the epithelial-mesenchymal transition (EMT)—a key process in tumor invasion and metastasis—by upregulating EMT transcription factors (e.g., Snail, Twist). Additionally, FOLR1 overexpression is linked to increased DNA repair capacity in cancer cells, contributing to chemoresistance to DNA-damaging agents such as platinum-based chemotherapy.
4. FOLR1 as a Therapeutic Target: Preclinical and Clinical Development
The cancer-specific overexpression and functional role of FOLR1 make it a highly promising target for anti-tumor therapy, with a diverse array of FOLR1-targeted strategies currently in preclinical and clinical development.
Preclinical Validation of FOLR1 Inhibition
In vitro and in vivo preclinical studies have consistently demonstrated that targeting FOLR1 inhibits tumor growth and progression:
- SiRNA-mediated FOLR1 knockdown in ovarian cancer cells significantly reduces cell proliferation, colony formation in soft agar, and invasive/migratory capacity—key hallmarks of cancer malignancy.
- FOLR1-neutralizing monoclonal antibodies block folate uptake and inhibit tumor growth in FOLR1-positive ovarian and breast cancer xenograft models, with minimal toxicity to normal tissues.
- Folate-drug conjugates (FDCs) and FOLR1-targeted ADCs selectively deliver cytotoxic payloads to FOLR1-positive tumor cells, inducing robust anti-tumor activity in preclinical models of ovarian and lung cancer.
Clinical Development of FOLR1-Targeted Therapeutics
Several FOLR1-targeted agents have advanced to clinical trials, with promising efficacy and safety profiles observed in FOLR1-positive cancer patients:
- Antibody-drug conjugates (ADCs): Mirvetuximab soravtansine, a FOLR1-targeted ADC consisting of a humanized anti-FOLR1 monoclonal antibody conjugated to a microtubule inhibitor, has shown significant clinical activity in platinum-resistant ovarian cancer, with durable responses and a favorable safety profile leading to its regulatory approval.
- Monoclonal antibodies: Humanized anti-FOLR1 antibodies (e.g., farletuzumab) are being evaluated in combination with chemotherapy and immunotherapy for ovarian and breast cancer, with early clinical data showing enhanced anti-tumor efficacy.
- Folate-drug conjugates: FDCs that link folate to cytotoxic drugs (e.g., methotrexate, paclitaxel) enable selective delivery of chemotherapy to FOLR1-positive tumor cells, reducing systemic toxicity.
- CAR-T cells: FOLR1-targeted CAR-T cells are in preclinical and early clinical development for ovarian and pancreatic cancer, harnessing the power of adoptive cell therapy to eliminate FOLR1-positive tumor cells.
Product Empowerment: ANT BIO’s High-Quality FOLR1 Recombinant Proteins (UA Sub-brand)
As a global leader in recombinant protein development and life science research solutions, ANT BIO PTE. LTD.—via its UA sub-brand (specializing in high-purity recombinant proteins and custom protein services)—offers a portfolio of biologically active FOLR1 recombinant proteins engineered for cutting-edge FOLR1 research and drug development. Produced in the HEK293 eukaryotic expression system—ensuring proper glycosylation, folding, and native biological activity—our FOLR1 proteins include human and mouse orthologs with optimized affinity tags (His, Avi, Fc) and biotinylation for versatile research applications. These high-quality FOLR1 recombinant proteins serve as critical research tools for validating FOLR1-targeted therapeutics, studying FOLR1-folate interactions, and elucidating the mechanistic role of FOLR1 in cancer—empowering researchers and biopharmaceutical companies to accelerate FOLR1-based oncology research and drug development.
Core Advantages of ANT BIO’s FOLR1 Recombinant Proteins
| Core Advantage | Detailed Description |
|---|---|
| Native Biological Activity & Proper Glycosylation | Produced in the HEK293 eukaryotic expression system to ensure post-translational glycosylation—an essential modification for FOLR1 folate-binding affinity and structural stability. All proteins retain high-affinity folate binding and native receptor activity, validated via functional binding assays. |
| Diverse Species and Tag Formats | Offer human and mouse FOLR1 recombinant proteins with flexible affinity tag combinations (His&Avi, Fc) and biotinylated variants, enabling compatibility with a wide range of experimental techniques (e.g., SPR, ELISA, pull-down assays, flow cytometry). |
| High Purity and Low Endotoxin | Purified via advanced affinity chromatography to achieve high purity (>95%) with low endotoxin levels (<1 EU/μg), ensuring minimal non-specific binding and cytotoxicity in cell-based assays and functional studies. |
| Biotinylated for High-Throughput Applications | Biotinylated FOLR1 variants (His&Avi tag) enable site-specific biotinylation and stable immobilization on streptavidin-coated surfaces, ideal for high-throughput screening (HTS) of FOLR1-targeted small molecules, antibodies, and drug conjugates. |
| Rigorous Quality Control (QC) Validation | Each batch undergoes comprehensive QC testing, including SDS-PAGE and Western blot for purity/identity, UV-Vis spectroscopy for concentration determination, and functional folate-binding assays for activity validation—ensuring batch-to-batch consistency and reliable experimental results. |
Key Application Scenarios for ANT BIO’s FOLR1 Recombinant Proteins
ANT BIO’s FOLR1 recombinant proteins are versatile, validated research tools for all aspects of FOLR1 research and oncology drug development, supporting both basic mechanistic studies and preclinical therapeutic development:
| Research Scenario | Experimental Value & Application |
|---|---|
| FOLR1 Binding Assays | Used in SPR, BLI, and ELISA to measure the binding affinity of anti-FOLR1 antibodies, folate analogs, and FOLR1-targeted drug conjugates—critical for lead compound optimization and therapeutic development. |
| High-Throughput Screening (HTS) | Biotinylated FOLR1 proteins are immobilized on streptavidin plates for HTS of small molecules, peptides, and antibodies that target FOLR1—enabling the rapid identification of novel FOLR1 inhibitors and binders. |
| Mechanistic Studies of FOLR1 Function | Serve as a recombinant substrate for studying FOLR1-folate interactions, receptor recycling, and FOLR1-mediated signaling in cell-free and cell-based assays—unraveling the molecular mechanisms of FOLR1 in cancer. |
| Antibody and ADC Development | Used as an immunogen and positive control for the development and validation of anti-FOLR1 monoclonal antibodies, bispecific antibodies, and ADCs—ensuring antibody specificity and functional binding to FOLR1. |
| Assay Development and Validation | Act as a gold-standard reference material for developing and validating FOLR1 detection assays (e.g., flow cytometry, IHC) for cancer diagnosis and prognostic stratification—ensuring assay accuracy and reproducibility. |
| In Vivo Preclinical Studies | Recombinant FOLR1 protein is used to validate FOLR1-targeted imaging agents and therapeutics in mouse xenograft models—enabling the assessment of in vivo target engagement and anti-tumor efficacy. |
Brand Mission
At ANT BIO PTE. LTD., our core mission is to empower life science research and biopharmaceutical development by providing high-quality, innovative, and reliable biological reagents, research tools, and comprehensive solutions. As a leading global provider of recombinant proteins, antibodies, and life science reagents, we have built three specialized sub-brands that cover the full spectrum of research and drug development needs, creating a seamless one-stop procurement experience for researchers, biotech companies, and pharmaceutical institutions worldwide:
- Absin: Specializes in general life science reagents and kits, including cell culture media, ELISA kits, SPR assay buffers, and molecular biology reagents—supporting the experimental workflows for FOLR1 research and drug development.
- Starter: Our flagship antibody specialist sub-brand, offering high-specificity anti-FOLR1 antibodies and custom antibody development services—complementing our FOLR1 recombinant proteins for comprehensive FOLR1 detection and targeting studies.
- UA: Dedicated to recombinant proteins and custom protein services, including our premium FOLR1 recombinant proteins (human/mouse, biotinylated/Fc-fused) and custom protein expression/purification—our core expertise in producing biologically active, post-translationally modified proteins for oncology and precision medicine research.
We are committed to investing in the development of high-quality recombinant proteins for emerging cancer therapeutic targets such as FOLR1, providing rigorous QC validation and professional technical support to help researchers overcome experimental challenges and accelerate the translation of basic science discoveries into clinical therapies. For ANT BIO, innovation is the core driving force, quality is the unshakable foundation, and customer-centricity is the eternal service concept—we strive to be your trusted partner in every step of your oncology research and drug development journey.
Related Product List: ANT BIO’s FOLR1 Recombinant Proteins (UA Sub-brand)
All products are biologically active FOLR1 recombinant proteins produced in HEK293 cells with proper glycosylation, rigorous QC validation for purity and activity, and available in human/mouse species with diverse tag/biotinylation formats.
| Catalog No. | Product Name | Host Species | Expression System | Conjugation / Tag | Price (USD) | Application |
|---|---|---|---|---|---|---|
| UA010834 | Biotinylated FOLR1 His&Avi Tag Protein, Human | Human | HEK293 | Biotin, His&Avi Tag | 410 | SPR, BLI, ELISA, HTS, Pull-down Assays |
| UA010117 | FOLR1 Fc Chimera Protein, Human | Human | HEK293 | Unconjugated, Fc Tag | 535 | Antibody Development, Flow Cytometry, Functional Assays |
| UA010437 | Biotinylated FOLR1 His&Avi Tag Protein, Mouse | Mouse | HEK293 | Biotin, His&Avi Tag | 410 | In Vivo Preclinical Studies, Mouse Model Assays, Cross-Species Research |
For detailed product specifications, bulk pricing, custom FOLR1 protein engineering services (e.g., mutant variants), or additional species formats, please visit the ANT BIO official website or contact our sales team for a personalized quote.
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ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs
At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.
