PCDH17 (Protocadherin 17), a 126 kDa calcium-dependent cell adhesion protein, belongs to the cadherin family and plays critical roles in neuronal connectivity and epithelial integrity . Its dysregulation is linked to cancers, including colorectal and breast, where it acts as a tumor suppressor . Antibodies targeting PCDH17 are essential for studying its expression, subcellular localization, and functional mechanisms.
HRP-conjugated PCDH17 antibodies combine the specificity of anti-PCDH17 antibodies with horseradish peroxidase (HRP), an enzyme that catalyzes oxidative reactions for colorimetric detection in assays like ELISA and Western blot. These conjugates enhance sensitivity and streamline workflows in immunodetection .
HRP-conjugated PCDH17 antibodies are engineered for high-performance detection in enzymatic assays. Key features include:
These antibodies are validated for specificity and sensitivity, with dilutions typically optimized per assay (e.g., 1:500–1:1000 for WB) .
Cancer Biology
PCDH17 antibodies identified its tumor-suppressive role in colorectal cancer (CRC), correlating with 5-fluorouracil (5-FU) sensitivity. High PCDH17 expression promoted apoptosis and autophagy, enhancing chemotherapeutic efficacy .
In breast cancer, PCDH17 promoter methylation linked to downregulation, suggesting epigenetic silencing drives tumorigenesis .
Mechanistic Insights
Limited Cross-Reactivity: Most HRP-conjugated PCDH17 antibodies target human PCDH17, limiting cross-species studies .
Optimal Dilution: Requires titration for each assay to avoid non-specific binding .
Epitope Specificity: Variability in immunogen regions (e.g., AA 39–89, AA 1050–1150) may affect detection outcomes .
PCDH17 (Protocadherin 17) is a 1,159 amino acid single-pass type I membrane protein containing six cadherin domains. It functions as a calcium-dependent cell adhesion protein that plays a crucial role in establishing cell-cell connections within brain tissue. The gene encoding PCDH17 maps to human chromosome 13, which houses over 400 genes, including BRCA2 and RB1, and comprises nearly 4% of the human genome . Recent research has revealed that PCDH17 functions as a tumor suppressor in colorectal cancer (CRC) and is frequently methylated in these cancers . The significance of PCDH17 in research has grown substantially as studies demonstrate its potential as a prognostic marker, particularly for predicting 5-fluorouracil (5-FU) sensitivity in CRC patients .
The PCDH17 Antibody, HRP conjugated is versatile for multiple research applications with specific recommended dilutions for optimal results. For Western Blot applications, a dilution range of 1:100-1000 is recommended to achieve optimal signal-to-noise ratio. For immunohistochemistry on paraffin-embedded tissues (IHC-P), a dilution range of 1:100-500 is suggested . These recommendations serve as starting points, and researchers should perform optimization procedures for their specific experimental conditions, including antibody titration, blocking optimization, and incubation time adjustments. The antibody demonstrates reactivity across human, mouse, and rat samples, making it suitable for comparative studies across these species .
To maintain optimal activity of PCDH17 Antibody, HRP conjugated, proper storage and handling procedures are critical. The antibody should be stored at -20°C for long-term preservation and at 4°C for short-term use (1-2 weeks). Avoid repeated freeze-thaw cycles, as these can significantly degrade the antibody and reduce its binding efficiency. When working with the antibody, aliquot into single-use volumes before freezing to prevent the need for multiple thaws. Always centrifuge the antibody vial briefly before opening to collect liquid at the bottom of the tube. For dilutions, use sterile buffers with pH compatibility for HRP activity (typically pH 6.8-7.5). Minimize exposure to light, as HRP conjugates can be photosensitive. During experimental procedures, maintain samples at appropriate temperatures (typically 4°C for storage of diluted antibody and room temperature for incubations) to ensure consistent performance across experiments.
When designing Western blot experiments with PCDH17 Antibody, HRP conjugated, a comprehensive control strategy should be implemented to ensure reliable and interpretable results. Include the following controls:
Positive Control: Cell lines or tissues with known PCDH17 expression (e.g., specific neural tissues or colorectal cancer cell lines with confirmed PCDH17 expression).
Negative Control: Samples lacking PCDH17 expression or samples from PCDH17 knockout models.
Loading Control: Use housekeeping proteins (β-actin, GAPDH, or α-tubulin) to normalize protein loading between samples.
Antibody Controls:
Molecular Weight Marker: To confirm the detected band corresponds to the expected molecular weight of PCDH17 (approximately 135-140 kDa).
Blocking Peptide Control: Pre-incubation of the antibody with the immunizing peptide should eliminate specific binding and the corresponding signal.
To validate PCDH17 knockdown or overexpression experiments, include samples with confirmed altered expression levels, as demonstrated in studies where PCDH17 expression was modulated using shRNA or overexpression vectors .
For optimal detection of PCDH17 in paraffin-embedded tissues using HRP-conjugated antibodies, the following methodological approach is recommended:
Tissue Preparation:
Fix tissues in 10% neutral buffered formalin for 24-48 hours
Process and embed in paraffin according to standard histological procedures
Section tissues at 4-5 μm thickness onto adhesive slides
Deparaffinization and Rehydration:
Xylene: 3 changes, 5 minutes each
100% ethanol: 2 changes, 3 minutes each
95%, 80%, 70% ethanol: 3 minutes each
Distilled water: 5 minutes
Antigen Retrieval (critical for PCDH17 detection):
Heat-induced epitope retrieval in citrate buffer (pH 6.0) at 95-98°C for 20 minutes
Allow slides to cool in buffer for 20 minutes at room temperature
Endogenous Peroxidase Blocking:
Incubate sections in 3% hydrogen peroxide in methanol for 15 minutes
Wash in PBS (3 × 5 minutes)
Non-specific Binding Blocking:
Incubate with 5% normal goat serum in PBS for 1 hour at room temperature
Primary Antibody Incubation:
Chromogenic Detection:
Apply DAB substrate solution for 5-10 minutes (monitor under microscope for optimal signal)
Wash in distilled water
Counterstaining and Mounting:
Counterstain with hematoxylin for 1-2 minutes
Dehydrate through graded alcohols
Clear in xylene and mount with permanent mounting medium
This protocol has been validated in studies examining PCDH17 expression in colorectal cancer tissues, where PCDH17 showed predominantly cytoplasmic localization in cancer cells .
PCDH17 Antibody, HRP conjugated can be effectively employed to investigate the relationship between PCDH17 expression and autophagy in cancer research through the following methodological approaches:
Co-detection of PCDH17 and Autophagy Markers:
Use PCDH17 Antibody, HRP conjugated in Western blots alongside autophagy markers like LC3B-II, BECN1 (Beclin-1), and p62/SQSTM1
In dual immunofluorescence or sequential IHC, coordinate PCDH17 detection with autophagy markers to assess co-localization or expression correlation
Autophagy Flux Analysis:
Treat cells with autophagy modulators (e.g., rapamycin, chloroquine) in the presence or absence of PCDH17 expression
Monitor changes in LC3B-II turnover and BECN1 expression in relation to PCDH17 levels
Use Western blot to quantify these changes with PCDH17 Antibody, HRP conjugated at 1:100-1000 dilution
Functional Studies:
Research has demonstrated that PCDH17 reexpression in colorectal cancer cells augments 5-FU sensitivity by promoting apoptosis and autophagic cell death. Studies showed that PCDH17 knockdown significantly inhibited LC3B-II turnover and the expression of BECN1, while BECN1 overexpression did not affect PCDH17 expression, indicating that PCDH17 modulates BECN1 and apoptosis .
PCDH17 expression demonstrates a significant positive correlation with chemosensitivity in colorectal cancer, particularly to 5-fluorouracil (5-FU) treatment. A comprehensive analysis of PCDH17 expression in chemosensitive and chemoresistant CRC tissues revealed several important patterns:
PCDH17 was significantly more highly expressed in 5-FU-sensitive CRC tissues (52.4%, 11/21 cases) compared to 5-FU-resistant tissues (7.7%, 2/39 cases) . This expression pattern was mirrored by BECN1 (autophagy-related protein), which showed high expression in 81% (17/21 cases) of chemosensitive tissues versus 30.8% (12/39 cases) in chemoresistant tissues .
The correlation between PCDH17 expression and clinical parameters revealed that high PCDH17 expression was significantly associated with reduced lymph node metastasis (pN0/1 categories) compared to advanced nodal involvement (pN2) (p=0.0109) . This relationship is detailed in the following table:
Clinical Parameter | N | High PCDH17 (%) | Low PCDH17 (%) | p value |
---|---|---|---|---|
pN categories | ||||
pN0/1 | 31 | 11 (35.5) | 20 (64.5) | 0.0109 |
pN2 | 29 | 2 (6.9) | 27 (93.1) | |
Chemosensitivity | ||||
Sensitive | 21 | 11 (52.4) | 10 (47.6) | <0.0001 |
Resistant | 39 | 2 (7.7) | 37 (92.3) |
Functionally, restoring PCDH17 expression in CRC cell lines significantly increased their sensitivity to 5-FU treatment, while PCDH17 knockdown attenuated 5-FU sensitivity in a dose-dependent manner . These findings collectively suggest that PCDH17 expression status could serve as a valuable predictive biomarker for 5-FU sensitivity in CRC patients.
The relationship between PCDH17 and autophagy in cancer cells is mediated through a complex molecular signaling cascade primarily involving the c-Jun NH2-terminal kinase (JNK) pathway. Several key mechanisms have been elucidated:
JNK Pathway Activation:
Autophagy Regulation:
PCDH17 expression positively regulates autophagy-related proteins, particularly increasing BECN1 (Beclin-1) expression and LC3B-II turnover
PCDH17 knockdown experiments demonstrated significant inhibition of LC3B-II turnover and BECN1 expression
Importantly, BECN1 overexpression did not affect PCDH17 expression, suggesting a unidirectional regulatory relationship
Experimental Validation:
Pharmacological inhibition of JNK using SP600125 (10 μM) in PCDH17-transfected CRC cells significantly decreased phosphorylated c-Jun levels and reduced the LC3-II/I ratio, without affecting PCDH17 expression
This confirms JNK's position downstream of PCDH17 but upstream of autophagy induction
PCDH17-induced autophagic cell death was attenuated when JNK was inhibited
5-FU Response Mechanism:
This mechanistic understanding provides valuable insights for targeted approaches in cancer therapy, particularly for enhancing chemosensitivity in colorectal cancer through modulation of the PCDH17-JNK-autophagy axis.
Dual-labeling experiments utilizing PCDH17 Antibody, HRP conjugated alongside JNK pathway markers provide powerful insights into their functional interactions. The following methodological approach enables comprehensive investigation of these relationships:
Sequential Immunohistochemistry (IHC) Protocol:
First staining round: Apply PCDH17 Antibody, HRP conjugated (1:100-500) and develop with DAB (brown)
Heat inactivation: Microwave slides in citrate buffer (pH 6.0) for 10 minutes
Second staining round: Apply antibodies against phospho-JNK or phospho-c-Jun and develop with Vector Blue
This approach enables visualization of spatial relationships between PCDH17 and activated JNK pathway components
Multiplex Immunofluorescence Strategy:
Convert HRP-conjugated PCDH17 Antibody to fluorescent signal using tyramide signal amplification
Counter-label with antibodies against JNK pathway components (p-JNK, p-c-Jun)
Include autophagy markers (LC3B, BECN1) to visualize the complete signaling axis
Employ confocal microscopy to assess co-localization patterns
Proximity Ligation Assay (PLA):
Use PCDH17 Antibody (after HRP inactivation) alongside JNK pathway antibodies
This technique reveals potential protein-protein interactions occurring within 40nm distance
Quantification of PLA signals provides insights into the molecular proximity of PCDH17 and JNK pathway components
Co-Immunoprecipitation Framework:
Use PCDH17 Antibody for immunoprecipitation followed by Western blotting for JNK pathway components
Alternatively, immunoprecipitate JNK pathway proteins and probe for PCDH17
Include appropriate controls (IgG control, input lysate)
Time-course Analysis Post-Treatment:
Treat cells with 5-FU at various time points (6h, 12h, 24h, 48h)
Perform dual-labeling to track the temporal relationship between PCDH17 expression and JNK activation
This reveals whether JNK activation precedes, follows, or occurs simultaneously with PCDH17 upregulation
Research has established that inhibition of JNK in PCDH17-transfected colorectal cancer cells significantly decreases phosphorylated c-Jun levels and reduces the LC3-II/I ratio without affecting PCDH17 expression, confirming JNK's position downstream of PCDH17 but upstream of autophagy induction . These dual-labeling approaches provide critical insights into the spatiotemporal dynamics of the PCDH17-JNK-autophagy signaling axis.
When encountering inconsistent PCDH17 staining patterns in immunohistochemistry experiments using HRP-conjugated antibodies, a systematic troubleshooting approach is essential:
Fixation and Processing Evaluation:
Inconsistent fixation times can significantly impact PCDH17 epitope availability
Monitor and standardize fixation duration (optimal: 24-48 hours in 10% neutral buffered formalin)
Assess tissue processing protocols, as excessive dehydration or clearing can denature PCDH17 protein
Antigen Retrieval Optimization:
PCDH17 detection often requires precise antigen retrieval conditions
Compare citrate buffer (pH 6.0) versus EDTA buffer (pH 9.0) for optimal epitope unmasking
Adjust retrieval time (15-30 minutes) and temperature (95-98°C) systematically
Document conditions that yield reproducible results for your specific tissue types
Antibody Dilution Matrix:
Positive Control Validation:
Technical Considerations:
Ensure even distribution of reagents across tissue sections
Minimize section drying during the staining procedure
Standardize washing steps (duration, buffer composition, agitation)
Consider automated staining platforms for improved consistency
Signal Enhancement Strategy:
For weak signals, implement tyramide signal amplification (TSA)
Increase DAB development time while monitoring under microscope
Adjust counterstaining intensity to improve signal-to-background ratio
Research has shown that PCDH17 localizes predominantly in the cytoplasm of colorectal cancer cells . Deviations from this pattern may indicate technical issues or biologically significant variations that warrant further investigation.
When evaluating PCDH17 expression as a predictive biomarker for chemosensitivity, researchers should be aware of several potential pitfalls that could affect data interpretation and clinical translation:
Intratumoral Heterogeneity Considerations:
PCDH17 expression can vary significantly across different regions within the same tumor
Single biopsy samples may not accurately represent the entire tumor's PCDH17 status
Recommendation: Analyze multiple tumor regions (minimum 3-5 areas) and report both the average and heterogeneity index
Scoring System Standardization:
Inconsistent scoring methods can lead to discrepant results between studies
Establish clear criteria for what constitutes "high" versus "low" PCDH17 expression
Consider both staining intensity and percentage of positive cells (e.g., H-score or Allred scoring)
The threshold used in published research (52.4% positivity in chemosensitive vs. 7.7% in chemoresistant tissues) should be validated in independent cohorts
Confounding Molecular Factors:
PCDH17 expression correlates with BECN1 levels, but other autophagy regulators may influence outcomes
Additional genetic alterations (e.g., JNK pathway mutations) could modify the PCDH17-chemosensitivity relationship
Consider multivariate analysis incorporating known colorectal cancer molecular subtypes
Technical Variables:
Pre-analytical variables (fixation time, tissue processing) can affect PCDH17 immunoreactivity
Antibody selection: polyclonal antibodies may show batch-to-batch variability
Detection systems (DAB vs. fluorescence) might yield different sensitivity levels
Clinical Context Limitations:
The predictive value of PCDH17 has been primarily established for 5-FU monotherapy
Modern treatment regimens often combine multiple agents (FOLFOX, FOLFIRI)
Validation studies should assess PCDH17's predictive value in current combination therapy settings
Alternative Mechanism Consideration:
While PCDH17 is linked to autophagy and JNK-dependent mechanisms, alternative pathways may contribute to chemosensitivity
PCDH17 methylation status may provide additional or complementary predictive information
Consider integrating multiple biomarkers for improved predictive accuracy
Research has shown a significant association between PCDH17 expression and 5-FU sensitivity (p<0.0001) , but these potential pitfalls should be addressed to establish PCDH17 as a robust clinical biomarker.
Distinguishing PCDH17-induced autophagy from general stress-induced autophagy requires sophisticated experimental designs and careful controls. The following methodological approaches can help researchers make this critical distinction:
Genetic Modulation Systems:
PCDH17 Knockdown in Stress Conditions: Apply 5-FU or other stressors to cells with and without PCDH17 knockdown via shRNA
Inducible PCDH17 Expression: Use Tet-On/Off systems to control PCDH17 expression independent of stress factors
Rescue Experiments: Reintroduce PCDH17 in knockout cells and assess if autophagy is restored specifically through PCDH17-dependent mechanisms
Research has shown that PCDH17 knockdown significantly inhibits LC3B-II turnover and BECN1 expression, confirming direct regulation
Pathway-Specific Inhibition:
JNK Pathway Blockade: Use SP600125 (10 μM) to specifically inhibit JNK and determine if PCDH17-induced autophagy is selectively affected
Control Stress Pathways: Simultaneously inhibit multiple stress response pathways (MAPK, p38, NF-κB) to isolate PCDH17-specific effects
Autophagy Stage Inhibition: Apply early (3-MA) vs. late (bafilomycin A1) autophagy inhibitors to characterize the stage specificity of PCDH17's effect
Data shows that inhibiting JNK in PCDH17-transfected cells specifically decreases the LC3-II/I ratio without affecting PCDH17 expression
Temporal Analysis:
Time-Course Experiments: Monitor autophagy markers at multiple time points post-stressor application
PCDH17 Expression Kinetics: Track the relationship between PCDH17 upregulation and autophagy induction
Pulse-Chase Analysis: Use LC3 turnover assays to determine if PCDH17 affects autophagy induction or flux
Molecular Interaction Studies:
Proximity Ligation Assays: Determine if PCDH17 directly interacts with autophagy machinery components
Co-Immunoprecipitation: Assess physical interactions between PCDH17, JNK pathway components, and autophagy proteins
Subcellular Fractionation: Analyze whether PCDH17 relocates to autophagosome formation sites during autophagy induction
Comparative Systems Biology:
Transcriptome Analysis: Compare gene expression patterns between PCDH17-induced and general stress-induced autophagy
Phosphoproteomics: Identify unique phosphorylation signatures in PCDH17-mediated autophagic responses
Metabolic Profiling: Assess whether PCDH17-induced autophagy has distinctive metabolic consequences
Research has demonstrated that autophagy plays a dominant role in PCDH17-induced cell death, as autophagy inhibitors blocked cell death to a greater extent than pancaspase inhibitors . This distinctive feature helps differentiate PCDH17-mediated autophagy from general stress responses and highlights its potential as a therapeutic target.
Several cutting-edge technologies are poised to revolutionize PCDH17 detection and functional analysis in cancer research, offering unprecedented resolution and insights:
Advanced Imaging Technologies:
Super-Resolution Microscopy: Techniques like STORM and PALM can visualize PCDH17 localization at nanometer resolution, potentially revealing previously undetectable subcellular distribution patterns
Lattice Light-Sheet Microscopy: Enables real-time visualization of PCDH17 trafficking and interactions with minimal phototoxicity in living cells
Spatial Transcriptomics: Combines PCDH17 protein detection with localized RNA expression analysis for comprehensive spatial context
Single-Cell Analysis Platforms:
Single-Cell Proteomics: Quantifies PCDH17 protein levels and associated pathway components at individual cell resolution
CyTOF/Mass Cytometry: Simultaneously measures PCDH17 alongside dozens of other cancer and immune markers without fluorescence spillover limitations
Cellular Indexing of Transcriptomes and Epitopes (CITE-seq): Links PCDH17 protein expression with transcriptomic profiles at single-cell resolution
Genome Editing and Screening:
CRISPR Base Editing: Introduces specific PCDH17 mutations without DNA double-strand breaks
CRISPR Activation/Interference (CRISPRa/CRISPRi): Modulates PCDH17 expression without altering the genetic sequence
CRISPR Screens: Systematically identifies genes that modify PCDH17-dependent chemosensitivity
Prime Editing: Enables precise introduction of clinically relevant PCDH17 mutations for functional characterization
Organoid and Patient-Derived Models:
Tumor Organoids: Creates patient-specific 3D models to test PCDH17's role in chemosensitivity
Microfluidic Tumor-on-a-Chip: Assesses PCDH17 functions in more physiologically relevant microenvironments
Humanized Mouse Models: Evaluates PCDH17-targeted therapies in the context of human immune components
Therapeutic Development Platforms:
Antibody-Drug Conjugates (ADCs): Utilizes PCDH17-targeting antibodies to deliver cytotoxic payloads specifically to cancer cells
mRNA Therapeutics: Temporarily restores PCDH17 expression in tumors with methylated PCDH17
Small Molecule Screens: Identifies compounds that modulate PCDH17-JNK-autophagy axis for enhanced chemosensitivity
These technologies could significantly advance our understanding of how PCDH17 expression correlates with chemosensitivity in colorectal cancer and potentially other malignancies, as evidenced by research showing PCDH17's role in promoting JNK-dependent autophagic cell death and enhancing 5-FU sensitivity .
Integration of PCDH17 status into personalized medicine frameworks for colorectal cancer represents a promising frontier that could significantly enhance treatment outcomes through several strategic approaches:
Diagnostic and Predictive Biomarker Implementation:
Companion Diagnostic Development: Create standardized IHC assays for PCDH17 expression to guide 5-FU-based therapy decisions
Multiparameter Biomarker Panels: Incorporate PCDH17 alongside established markers (MSI status, RAS/RAF mutations) for comprehensive profiling
Liquid Biopsy Applications: Develop methods to detect PCDH17 methylation patterns in circulating tumor DNA
Research has established significant correlations between PCDH17 expression and 5-FU sensitivity (p<0.0001), providing strong rationale for its clinical implementation
Therapy Selection Algorithms:
Treatment Decision Trees: Develop algorithms incorporating PCDH17 status to guide chemotherapy selection
Combination Therapy Stratification: Determine if PCDH17 status predicts response to 5-FU in combination with targeted agents (anti-EGFR, anti-VEGF)
Alternative Pathway Selection: For PCDH17-low tumors, recommend therapies targeting alternative pathways
Clinical Trial Design and Patient Stratification:
Biomarker-Guided Trials: Design trials that prospectively stratify patients based on PCDH17 expression
Adaptive Trial Designs: Incorporate PCDH17 testing in basket or umbrella trials to refine patient selection
Post-Hoc Analyses: Retrospectively analyze PCDH17 status in completed trials to validate its predictive value
Epigenetic Modulation Strategies:
Demethylating Agent Combinations: For tumors with methylated PCDH17, explore combining demethylating agents with conventional chemotherapy
Histone Deacetylase Inhibitors: Test if epigenetic modifiers can restore PCDH17 expression in resistant tumors
Targeted Demethylation: Develop CRISPR-based approaches for locus-specific PCDH17 demethylation
Monitoring and Resistance Management:
Serial PCDH17 Assessment: Monitor changes in PCDH17 expression during treatment to detect emerging resistance
Alternative Pathway Activation: Screen for bypass mechanisms in PCDH17-positive tumors that develop resistance
Adaptive Therapy Protocols: Adjust treatment intensity based on dynamic PCDH17 expression
Developing PCDH17-targeted therapies to enhance chemosensitivity faces several complex challenges that span basic science, translational research, and clinical implementation domains:
Biological Complexity Challenges:
Target Specificity: PCDH17 belongs to the protocadherin family with multiple homologous members, creating potential off-target effects
Context-Dependent Function: PCDH17's role may vary across cancer types and even within different regions of the same tumor
Compensatory Mechanisms: Cancer cells might activate alternative pathways to circumvent PCDH17-mediated effects
Pathway Redundancy: Multiple inputs regulate autophagy beyond the PCDH17-JNK axis, potentially limiting therapeutic efficacy
Therapeutic Development Hurdles:
Protein Restoration Challenge: As a tumor suppressor gene, developing therapeutics to restore PCDH17 function is more difficult than inhibiting oncogenic targets
Epigenetic Targeting: Selective demethylation of PCDH17 without affecting other genes remains technically challenging
Antibody Accessibility: PCDH17's membrane localization may not be uniformly accessible in solid tumors due to physical barriers
Delivery Systems: Targeting deep-seated tumors with PCDH17-modulating agents requires advanced delivery technologies
Clinical Translation Obstacles:
Patient Selection: Identifying optimal candidates for PCDH17-targeted therapy requires validated biomarker assays
Treatment Sequencing: Determining whether PCDH17 modulation should precede, accompany, or follow conventional chemotherapy
Resistance Monitoring: Developing methods to track adaptation to PCDH17-targeted interventions
Combination Toxicity: Managing potential synergistic toxicities when combining PCDH17 modulators with conventional chemotherapy
Technical and Methodological Limitations:
Model Systems: Current preclinical models may not fully recapitulate the complexity of PCDH17 regulation in human tumors
Functional Readouts: Standardizing methods to assess successful PCDH17 modulation in clinical specimens
Pharmacodynamic Markers: Identifying reliable indicators of on-target engagement for PCDH17-directed therapies
Long-term Effects: Understanding delayed consequences of manipulating PCDH17-mediated autophagy
Regulatory and Commercial Considerations:
Novel Endpoint Requirements: Regulatory approval may require innovative endpoints beyond traditional response criteria
Companion Diagnostic Development: Synchronized development of therapeutics and diagnostics adds complexity
Market Positioning: Determining how PCDH17-targeted approaches would complement or compete with established therapies