Pathology Model-Based Target
Validation
- The Most
Effective Approach to Obtain Evidence for Clinical Relevance of a Target
Purpose: Through
ISH/IHC analyses on tissue or cell line sections, to obtain evidence for the
speculated involvement of a RNA or protein molecule in a disease process.
Help to
eliminate non-disease relevant targets early and
cheaply.
Tissue array-based pathology model: The name is mainly referred to a
tissue array that consists of tissues relevant to a process or a pathological
feature of a disease or a group of pathological conditions. The tissues are
purposely selected and arranged in a way that allows easy comparison,
correlation and understanding of the expression patterns of the target and the
disease process under investigation.
Benefits: With pathology knowledge and careful ISH or IHC analysis
of a target on selected pathology models, it is possible to obtain:
1. Correlative data thorough observation of: cellular localization
(origin), level and normal Vs diseased cell expression pattern of a
target.
2. Potential causative data through analyses: a) target expression
pattern and microenvironments such as involved cells, extent, morphology
alterations, et al; b) dynamic association of a target with a disease
process, such as from acute to chronic, from pre-malignant to malignant, from
low grade to high grade, between good response and poor response; c)
relationship between the tested target and any other relevant molecules in the
same disease process by analyzing these molecules in the same sections and at
the same time.
3. Preclinical assessment: for antibody therapeutics safety
evaluation, it is essential to know the distribution pattern of a target or
existence of a cross-reactivity of a antibody therapeutics in human tissues.
Example 1
of pathology model-based target validation.
Example
2 of pathology model-based target validation. |
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