Leading ADC Targets in Oncology: Signaling Mechanisms and Therapeutic Advances
Leading ADC Targets in Oncology: Signaling Mechanisms and Therapeutic Advances
Antibody–drug conjugates (ADCs) use tumor cell-surface antigens to achieve antibody recognition and payload delivery. HER2, TROP2, Nectin-4, FRα, and c-Met have received substantial clinical validation, while HER3, B7-H3, CLDN18.2, and DLL3 continue to enter ADC development pipelines. The biological function, tumor selectivity, internalization capacity, and tissue distribution of each target provide distinct foundations for ADC development.
Keywords: ADC; HER2; TROP2; Nectin-4; FRα; c-Met; HER3; B7-H3; CLDN18.2; DLL3; tumor targets
1 Biological Basis of ADC Targets
1.1 ADC Targets and Conventional Tumor Targets
(1) Conventional Targets Depend on Oncogenic Driver Functions
Conventional targeted therapies generally inhibit driver proteins or signaling pathways that sustain tumor growth. For example, HER2 amplification can enhance PI3K–AKT and RAS–MAPK signaling, whereas aberrant MET activation can promote tumor cell proliferation, migration, and invasion.
Figure 1. Hallmarks of Cancer and Representative Therapeutic Targets
(2) ADC Targets Emphasize Delivery Capacity
An ADC target does not necessarily need to be a central oncogenic driver. A membrane protein can support payload delivery if it provides sufficient tumor cell-surface expression, antibody accessibility, and internalization capacity. HER2 and c-Met function as both signaling and delivery targets, whereas the ADC value of Nectin-4 and CLDN18.2 is derived more from tumor-selective expression or specialized tissue localization.
1.2 Key Selection Criteria for ADC Targets
(1) Tumor Cell-Surface Expression
ADCs must first recognize antigens displayed on the plasma membrane. High and stable tumor cell-surface expression supports antibody binding and ADC uptake and provides the basis for effective payload delivery.
(2) Tumor Selectivity
Target expression in normal tissues may produce on-target/off-tumor toxicity. Target evaluation should compare expression levels, tissue distribution, and epitope accessibility between tumors and normal tissues rather than relying solely on high expression within tumor specimens.
(3) Internalization and Intracellular Trafficking
Following target binding, an ADC generally undergoes internalization and endosomal–lysosomal trafficking, after which linker cleavage or antibody degradation releases the payload. Internalization efficiency, intracellular trafficking, and extracellular domain shedding can all affect effective payload delivery.
2 Clinically Validated ADC Targets
2.1 HER2/ERBB2
(1) HER2-Driven Signaling
HER2 belongs to the ErbB receptor tyrosine kinase family and can undergo gene amplification or protein overexpression in breast cancer, gastric cancer, and certain lung cancers. Although HER2 lacks a well-defined classical ligand, it has strong dimerization capacity and forms a particularly active heterodimer with HER3.
(2) Activation of PI3K–AKT and RAS–MAPK
HER2 dimerization enhances PI3K–AKT–mTOR and RAS–RAF–MEK–ERK signaling, promoting tumor cell proliferation, survival, and treatment resistance and establishing HER2 as a defined oncogenic driver.
(3) HER2 as an ADC Delivery Entry Point
HER2 provides stable membrane localization and a mature foundation for antibody recognition. Antibody binding and internalization can deliver ADC payloads into tumor cells. The development of Trastuzumab emtansine (T-DM1) clinically validated HER2 as an ADC target.
(4) Expansion into HER2-Low Tumors
Through efficient payload delivery and a bystander effect, Trastuzumab deruxtecan (T-DXd) reduces dependence on uniformly high HER2 expression. HER2-directed ADC therapy has consequently expanded from conventional HER2-positive disease into HER2-low tumors.
2.2 TROP2/TACSTD2
(1) Biological Functions of TROP2 in Cancer
TROP2 is a type I transmembrane glycoprotein encoded by TACSTD2 and is aberrantly expressed in multiple epithelial malignancies, including breast, lung, and gastrointestinal cancers. TROP2 participates in Ca²⁺ signaling and is associated with oncogenic networks such as PI3K–AKT and MAPK/ERK.
(2) Promotion of Malignant Tumor Phenotypes
Aberrant TROP2 expression can influence tumor cell proliferation, migration, invasion, and survival. Its protumor functions vary according to tumor type and cellular context.
(3) Broad Cell-Surface Expression as an ADC Advantage
Compared with classical driver receptors such as HER2, the principal ADC value of TROP2 derives from its broad cell-surface expression across epithelial tumors, providing potentially extensive patient coverage.
(4) Target Validation Across Different Payload Systems
Sacituzumab govitecan and Datopotamab deruxtecan use different linker–payload systems to target TROP2, demonstrating that the target can consistently support cytotoxic payload delivery.
2.3 Nectin-4
(1) Cell-Adhesion Function
Nectin-4 is an immunoglobulin superfamily cell-adhesion molecule involved in cell–cell junctions and maintenance of epithelial tissue architecture.
(2) Tumor-Associated Signaling Changes
In certain tumor models, aberrant Nectin-4 expression is associated with changes in PI3K–AKT, Rac1, and Wnt/β-catenin signaling and may influence migration, invasion, and epithelial–mesenchymal transition.
(3) Differential Expression Between Tumors and Normal Tissues
Nectin-4 shows relatively high cell-surface expression in urothelial carcinoma but comparatively restricted expression in most adult normal tissues. This difference provides a basis for selective ADC delivery.
(4) Nectin-4-Mediated MMAE Delivery
Enfortumab vedotin uses Nectin-4 for antibody binding and internalization and subsequently releases MMAE intracellularly. It represents a mature ADC strategy based on a membrane protein that is not a classical oncogenic driver.
2.4 FRα/FOLR1
(1) Folate Uptake and Metabolic Support
Folate receptor α (FRα/FOLR1) is a GPI-anchored membrane protein that binds folate with high affinity and participates in folate uptake through internalization, supporting one-carbon metabolism, nucleotide synthesis, and cell proliferation.
(2) Tumor-Associated Signal Regulation
FRα has also been linked to JAK–STAT3 and ERK1/2 signaling and may contribute to the proliferation and survival of certain tumor cells.
(3) Tumor Selectivity and Internalization
FRα is highly expressed in subsets of ovarian cancer and other gynecological malignancies, while antibody accessibility in most normal tissues is relatively limited. Its internalization capacity further supports its use as an ADC delivery entry point.
(4) Expression Quantification and Patient Selection
The development of Mirvetuximab soravtansine incorporated FRα membrane-staining intensity and the proportion of positive tumor cells into patient selection, making FRα an important model for quantitative ADC target assessment and companion diagnostics.
2.5 c-Met/MET
(1) Activation of HGF–c-Met Signaling
c-Met is a receptor tyrosine kinase encoded by MET. HGF binding induces c-Met phosphorylation and signal transmission through adaptor proteins such as GAB1 and GRB2.
(2) Downstream Oncogenic Networks
c-Met activates PI3K–AKT–mTOR, RAS–RAF–MEK–ERK, STAT3, and SRC/FAK signaling networks, promoting tumor cell proliferation, survival, migration, epithelial–mesenchymal transition, and invasion.
(3) Conventional MET Molecular Stratification
MET exon 14 skipping and gene amplification are important molecular bases for conventional MET-targeted therapy, which emphasizes oncogenic genomic alterations and signaling dependency.
(4) c-Met Protein Expression and ADC Stratification
c-Met-directed ADCs focus more strongly on cell-surface protein expression. Telisotuzumab vedotin uses c-Met to deliver MMAE, establishing high c-Met expression as a patient-selection approach distinct from traditional MET driver alterations.
3 Emerging ADC Targets
3.1 HER3/ERBB3
(1) Limited Intrinsic Kinase Activity
HER3 belongs to the ErbB family but has limited intrinsic kinase activity and generally requires heterodimerization with HER2, EGFR, or other receptors to transmit signals effectively.
(2) The HER2–HER3–PI3K–AKT Axis
The intracellular region of HER3 contains multiple PI3K-recruitment sites, allowing the HER2–HER3 complex to activate PI3K–AKT signaling efficiently and support tumor cell survival.
(3) Bypass Resistance
HER3 participates in the restoration of bypass signaling following EGFR- or HER2-targeted therapy, making it an important node in several mechanisms of tumor resistance.
(4) Value in ADC Development
Conventional kinase inhibitors cannot readily exploit the limited intrinsic kinase activity of HER3. ADCs require only sufficient cell-surface expression and internalization capacity for payload delivery. Patritumab deruxtecan has consequently transformed HER3 from a resistance-associated receptor into an ADC target.
3.2 B7-H3/CD276
(1) High Expression Across Multiple Solid Tumors
B7-H3 is a B7-family transmembrane protein that can be aberrantly overexpressed in lung, prostate, breast, and numerous other solid tumors, providing a broad target foundation for antibody recognition and ADC delivery.
(2) Immunoregulatory Functions
The complete receptor system and physiological regulatory mechanisms of B7-H3 have not been fully defined, but its aberrant expression is considered to be associated with tumor immune evasion.
(3) Oncogenic Signaling Networks
Current evidence also links abnormal B7-H3 expression with PI3K–AKT, JAK–STAT3, MAPK, and NF-κB signaling and suggests potential roles in epithelial–mesenchymal transition, invasion, metabolic reprogramming, and angiogenesis.
(4) Pan-Tumor ADC Potential
Cell-surface expression of B7-H3 across multiple solid tumors provides the potential for broad patient coverage. ADCs such as Ifinatamab deruxtecan are advancing B7-H3 as a pan-solid-tumor ADC target.
3.3 CLDN18.2
(1) Stomach-Specific Epithelial Localization
CLDN18.2 is a stomach-specific isoform of Claudin 18 that contributes to tight junctions, epithelial barrier function, and maintenance of cell polarity in the gastric epithelium.
(2) A Non-Classical Driver Target
Unlike HER2 or c-Met, CLDN18.2 does not drive continuous tumor growth through a classical kinase-signaling pathway. Its ADC value instead arises primarily from its specialized tissue localization.
(3) Epitope Exposure After Malignant Transformation
In normal gastric mucosa, CLDN18.2 is mainly confined within tight-junction structures, limiting antibody accessibility to its extracellular epitopes. Malignant transformation disrupts epithelial architecture and cell polarity, increasing exposure of these epitopes on the tumor cell surface.
(4) Tissue Selectivity and the Therapeutic Window
Restricted epitope accessibility in normal tissues and increased exposure in tumors provide a basis for the selective therapeutic window of CLDN18.2-targeted antibodies and ADCs.
3.4 DLL3
(1) Negative Regulation of Notch
DLL3 belongs to the Delta-like ligand family. Unlike canonical Notch-activating ligands such as DLL1 and DLL4, DLL3 primarily acts as a negative regulator of Notch by restricting receptor trafficking and signal transmission.
(2) ASCL1 and DLL3 Expression
The neuroendocrine transcription factor ASCL1 promotes DLL3 expression in small-cell lung cancer, linking DLL3 to neuroendocrine differentiation programs.
(3) Maintenance of the Neuroendocrine Phenotype
Elevated DLL3 expression is closely associated with suppressed Notch signaling and maintenance of the neuroendocrine phenotype. DLL3 is highly expressed in small-cell lung cancer and certain high-grade neuroendocrine tumors.
(4) Distinguishing the Target from the Therapeutic Platform
The early DLL3 ADC Rovalpituzumab tesirine did not achieve sustained clinical success. However, subsequent validation of DLL3 on other therapeutic platforms demonstrates that failure of a specific drug platform should not be interpreted as evidence that the target itself lacks therapeutic value.
3.5 B7-H4 and CDH17
(1) B7-H4
B7-H4 is an immunoregulatory membrane protein that can be aberrantly expressed in ovarian, breast, endometrial, and other cancers. B7-H4 can reduce T-cell proliferation, cytokine production, and effector functions and thereby promote tumor immune evasion. Its tumor-associated membrane expression has also led to its development as a delivery target for ADCs and other antibody-based therapeutics.
(2) CDH17
CDH17 is a cell-adhesion protein associated with gastrointestinal epithelial differentiation and can be highly expressed in colorectal, gastric, and other gastrointestinal cancers. Some studies link CDH17 with regulation of Wnt/β-catenin signaling and tumor cell proliferation, stemness, migration, and invasion. Its relatively concentrated expression in gastrointestinal tumors and membrane localization make CDH17 an emerging ADC target for digestive system malignancies.
4 Development Logic of Different ADC Targets
4.1 Oncogenic Signaling Targets
HER2 and c-Met have well-defined receptor tyrosine kinase signaling functions and can both directly support tumor growth and act as ADC delivery entry points. Although HER3 has limited intrinsic kinase activity, it participates in PI3K–AKT signaling and bypass resistance through heterodimerization, creating an ADC application distinct from conventional kinase inhibition.
4.2 Cell-Surface Expression and Internalization Targets
The ADC value of TROP2 and Nectin-4 depends more heavily on tumor cell-surface expression, antibody accessibility, and internalization capacity. These targets do not need to function as central drivers of tumor growth.
4.3 Tissue-Restricted and Epitope-Accessibility Targets
The therapeutic windows of FRα and CLDN18.2 are closely associated with tissue distribution. FRα development emphasizes tumor expression and internalization, whereas CLDN18.2 highlights the difference between restricted epitope accessibility in normal gastric mucosa and increased epitope exposure in tumors.
4.4 Immune- and Lineage-Associated Targets
B7-H3 and B7-H4 have immunoregulatory characteristics, whereas DLL3 is associated with the neuroendocrine lineage and Notch suppression. ADC development for these targets primarily exploits tumor-associated cell-surface expression rather than complete dependence on classical oncogenic driver signaling.
Target | Major Biological Pathway or Function | Principal Role in Tumors | Core Basis for ADC Development |
HER2 | PI3K–AKT–mTOR and RAS–MAPK | Proliferation, survival, and treatment resistance | Combined oncogenic driver and delivery entry point |
TROP2 | Ca²⁺, PI3K–AKT, MAPK, and related signaling | Proliferation, migration, and invasion | Broad cell-surface expression across epithelial tumors |
Nectin-4 | Cell adhesion; association with PI3K–AKT and Rac1 | Adhesion, migration, and EMT | Differential expression between tumors and normal tissues |
FRα | Folate uptake, JAK–STAT3, and ERK | Metabolic support and proliferation | Internalization capacity and expression-based stratification |
c-Met | PI3K–AKT, MAPK, STAT3, and SRC/FAK | Proliferation, EMT, and invasion | Protein expression can be used independently of driver mutations |
HER3 | HER2–HER3–PI3K–AKT | Survival and bypass resistance | Converts a difficult-to-inhibit receptor into a delivery entry point |
B7-H3 | Immune regulation and multiple oncogenic signaling networks | Immune evasion, invasion, and metabolic regulation | Cell-surface expression across multiple solid tumors |
CLDN18.2 | Tight junctions and cell polarity | Aberrant localization and epitope exposure after malignant transformation | Tissue selectivity and antibody accessibility |
DLL3 | Negative regulation of Notch and association with ASCL1 | Maintenance of the neuroendocrine phenotype | Selective cell-surface expression in small-cell lung cancer |
B7-H4 | T-cell immunosuppression | Immune evasion | Tumor-associated membrane expression |
CDH17 | Cell adhesion and association with Wnt/β-catenin | Proliferation, stemness, and migration | Relatively concentrated expression in gastrointestinal tumors |
In addition to these targets, CEACAM5, NaPi2b/SLC34A2, LIV-1/SLC39A6, PTK7, ROR1, PSMA/FOLH1, MUC1, and Tissue Factor have entered different stages of ADC research. Their development is based on various combinations of oncogenic signaling, cell-surface expression, internalization capacity, and differences in antigen accessibility between tumors and normal tissues.
5 Research Progress in Representative ADC Targets
5.1 Trastuzumab Deruxtecan
(1) HER2-Mediated DXd Delivery
Trastuzumab deruxtecan (T-DXd) uses HER2 for antibody binding and internalization and releases a topoisomerase I inhibitor payload, allowing HER2 to function as a tumor-selective delivery entry point.
(2) Bystander Effect
The DXd payload is membrane-permeable and can diffuse into adjacent tumor cells with lower HER2 expression, producing a bystander effect and reducing the dependence of ADC-mediated killing on uniformly high HER2 expression.
(3) Expansion of the HER2 Expression Range
T-DXd has expanded HER2-directed ADC therapy from conventional HER2-positive disease into lower-expression categories such as HER2-low tumors. Clinical assessment of HER2 is consequently shifting from a simple positive/negative classification toward a continuous expression spectrum.
5.2 Sacituzumab Govitecan and Datopotamab Deruxtecan
(1) Validation of TROP2 Targetability
The clinical application of Sacituzumab govitecan validated TROP2 as a druggable ADC target and demonstrated that a broadly expressed epithelial membrane protein can be transformed into a mature drug-delivery entry point.
(2) Expansion Across Different Payload Systems
Subsequent agents such as Datopotamab deruxtecan continue to target TROP2 using different linker–payload systems. Research is increasingly focused on target expression across tumor types, payload sensitivity, bystander effects, and therapeutic windows.
5.3 Enfortumab Vedotin
(1) Nectin-4-Mediated MMAE Delivery
Enfortumab vedotin uses Nectin-4 for antibody binding, internalization, and MMAE delivery and has clinically validated Nectin-4 as an ADC target in urothelial carcinoma.
(2) Dynamic Target Changes After Treatment
With broader therapeutic use, reduced Nectin-4 expression, changes in tumor cell phenotype, and antigen heterogeneity have become important directions in resistance research. Target assessment is consequently expanding from static pretreatment expression to dynamic changes under therapeutic pressure.
5.4 Mirvetuximab Soravtansine
(1) FRα-Mediated DM4 Delivery
Mirvetuximab soravtansine binds and internalizes through FRα to deliver DM4, directly translating FRα membrane localization and internalization capacity into therapeutic value.
(2) FRα Quantification and Patient Stratification
FRα membrane-staining intensity, the proportion of positive tumor cells, and the analytical method can all influence patient classification. FRα has consequently developed from a general tumor-associated antigen into a therapeutic biomarker requiring companion diagnostic support.
5.5 Telisotuzumab Vedotin
(1) High c-Met Expression as an ADC Selection Criterion
Telisotuzumab vedotin uses cell-surface c-Met to deliver MMAE, with patient selection placing greater emphasis on c-Met protein expression.
(2) Distinction from Conventional MET Molecular Stratification
Conventional MET inhibitors primarily target driver alterations such as MET exon 14 skipping and amplification. An ADC can instead use high c-Met protein expression to define a distinct treatment population, expanding the therapeutic use of receptor tyrosine kinase targets.
5.6 HER3, B7-H3, and CLDN18.2 ADCs
(1) HER3 ADCs
Patritumab deruxtecan uses HER3 cell-surface expression and internalization to deliver its payload, allowing a resistance-associated receptor to be targeted despite its limited intrinsic kinase activity.
(2) B7-H3 ADCs
Agents such as Ifinatamab deruxtecan continue to evaluate B7-H3 expression thresholds, potential patient coverage, and therapeutic windows across different solid tumors.
(3) CLDN18.2 ADCs
CLDN18.2 ADCs such as CMG901 exploit epitope exposure and tissue selectivity in gastric and related cancers, representing an ADC target-development pathway distinct from classical oncogenic driver receptors.
6 Products
6.1 Products for Research on Clinically Validated ADC Targets
Catalog # | Product Name/Description | Grade & Purity | Target and Research Positioning |
Trastuzumab (anti-HER2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, PBS Only, ≥95% (SDS-PAGE & SEC-HPLC), See COA | HER2-targeting antibody used in HER2-binding and ADC antibody-component research | |
Pertuzumab (anti-HER2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥95% (SDS-PAGE & SEC-HPLC), See COA | HER2-targeting antibody used in HER2 receptor and epitope research | |
Disitamab vedotin (anti-HER2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC), See COA | HER2-targeting ADC used in MMAE delivery research | |
Trastuzumab deruxtecan (anti-ERBB2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC) | HER2-targeting DXd ADC used in HER2-low and bystander-effect research | |
Trastuzumab emtansine (anti-ERBB2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC), See COA | HER2-targeting DM1 ADC used in HER2 ADC research | |
Sacituzumab govitecan (anti-TROP2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC), See COA | TROP2-targeting ADC used in TROP2-mediated SN-38 delivery research | |
Enfortumab vedotin-ejfv (anti-Nectin-4) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC), See COA | Nectin-4-targeting ADC used in receptor internalization and payload-delivery research | |
Mirvetuximab (anti-FOLR1) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥95% (SDS-PAGE & SEC-HPLC), See COA | FRα-targeting antibody used in FOLR1 expression and ADC antibody-component research | |
Telisotuzumab vedotin (anti-c-Met) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC), See COA | c-Met-targeting ADC used in research on tumors with high c-Met expression |
6.2 Products for Research on Emerging ADC Targets
Catalog # | Product Name/Description | Grade & Purity | Target and Research Positioning |
Recombinant HER3/ErbB3 Antibody | Recombinant, ExactAb™, Validated, 0.6 mg/mL | Detects HER3; used in HER3 expression and ADC target-validation research | |
Recombinant Human ErbB3/HER3 Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, His Tag, PBS Only, ≥90% (SDS-PAGE) | HER3 target protein used in HER3–antibody binding research | |
Patritumab (anti-ERBB3) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥95% (SDS-PAGE & SEC-HPLC), See COA | HER3-targeting antibody used in HER3 binding and internalization research | |
Patritumab deruxtecan (anti-ERBB3) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥90% (SDS-PAGE & SEC-HPLC), See COA | HER3-targeting ADC used in HER3-mediated payload-delivery research | |
Recombinant Human CD276 Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, Azide Free, His Tag, ≥95% (SDS-PAGE) | B7-H3/CD276 target protein used in B7-H3 target validation and antibody-binding research | |
Zolbetuximab (anti-CLDN18.2) | Animal Free, Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, Validated, ≥95% (SDS-PAGE & SEC-HPLC), See COA | CLDN18.2-targeting antibody used in CLDN18.2 target-validation and antibody-binding research |
6.3 Products for ADC Construction Research
Catalog # | Product Name/Description | Grade & Purity | Mechanism and Research Positioning |
Val-Cit | Moligand™, ≥98% | Protease-sensitive dipeptide used in cleavable ADC linker research | |
Mc-Val-Ala-PAB | ≥98% | Val-Ala-PAB-type cleavable linker used in ADC conjugation research | |
N-Succinimidyl 4-(N-Maleimidomethyl) cyclohexanecarboxylate(SMCC) | ≥98% (HPLC) | Non-cleavable crosslinker used to connect antibodies with payloads | |
DBCO-Maleimide | Moligand™, ≥95% | Used in copper-free click chemistry and cysteine conjugation | |
MonoMethyl auristatin E | Moligand™, ≥97% | MMAE microtubule-inhibiting payload used in ADC cytotoxicity research | |
MMAF | Moligand™, ≥95% | MMAF payload used in research on low-membrane-permeability cytotoxic payloads | |
Mertansine (DM1 Compound) | ≥98% | DM1-class maytansinoid payload used in microtubule-inhibiting ADC research | |
DM4 | ≥98% | Maytansinoid payload used in research on FRα and related ADCs | |
Mc-MMAE | ≥96% | MMAE linker–payload used in thiol-conjugated ADC construction | |
Ac-Lys-Val-Cit-PABC-MMAE | ≥99% | Cleavable MMAE linker–payload used in protease-triggered release research | |
Amino-PEG4-GGFG-Dxd | ≥99% | DXd linker–payload used in topoisomerase I inhibitor ADC construction | |
Propargyl-PEG4-GGFG-DXd | ≥99% | Click-compatible DXd linker–payload used in topoisomerase I inhibitor ADC research | |
Val-Ala-PABC-Exatecan | ≥99% | Exatecan linker–payload used in topoisomerase I inhibitor ADC research | |
MC-SN38 | ≥98% | SN-38 linker–payload used in TROP2 ADC construction research | |
SMCC-DM1 | ≥95% | Non-cleavable DM1 linker–payload used in T-DM1-type ADC research |
The development value of an ADC target is determined by its tumor biological function, membrane expression, internalization capacity, and tissue selectivity. Clinically validated targets have established multiple ADC development pathways, while emerging targets are expanding the use of resistance-associated receptors, immunoregulatory molecules, and tissue-restricted antigens.
References
[1] Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021;18:327–344.
[2] Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–137.
[3] Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9–20.
[4] Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384:1529–1541.
[5] Powles T, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med. 2024;390:875–888.
[6] Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-high platinum-resistant ovarian cancer. N Engl J Med. 2023;389:2162–2174.
[7] Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11:834–848.
[8] Nawaz FZ, Kipreos ET. Emerging roles for folate receptor FOLR1 in signaling and cancer. Trends Endocrinol Metab. 2022;33:159–174.
[9] Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 2015;7:302ra136.
[10] Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022;7:93.
For more related articles, please see below:
[1] Common Reducing Agents in Antibody–Drug Conjugates (ADCs)
[3] Antibody-coupled drug ADCs: Precise guidance, cancer destruction