Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 25 |
| Updated: | 4/6/2019 |
| Start Date: | September 7, 2004 |
| End Date: | August 11, 2014 |
This study will construct tissue microarrays (TMAs) pertaining to childhood cancer. TMA
technology is a recently developed one that allows for evaluating hundreds of tissue samples
simultaneously on the DNA, RNA, and protein levels. The goal is to identify a potential
molecular signature. Cancer drug discovery is currently focused on identifying drugs targeted
at the molecular level. Such drugs would be more selective and specific for proteins and
signaling pathways that are directly involved in the origin of tumors. However, the origin of
cancer among adults differs from that of cancer diagnosed in children. The overall approach
by the pharmaceutical industry in developing drugs is not likely to be aimed at low-incidence
cancers, such as childhood cancers. Thus, the researchers in this study propose to create a
childhood cancer TMA that include specimens from a wide range of solid tumors that present a
poor prognosis for patients. This TMA would in turn be used to identify antibodies and lead
to developing molecularly targeted drugs that would reach clinical trials in adults.
TMAs are created robotically. Small tissue cores are taken from paraffin-embedded tissue
blocks and are implanted into new paraffin blocks. The recipient blocks are then processed to
produce several hundred specimens that can be evaluated on a single glass slide. Specimens
representing 17 distinct kinds of pediatric solid tumors will be used in this study. Also
included will be samples of plexiform neurofibroma-that is, benign growths of nervous and
connective tissues.
Tissue specimens will come from patients who were age 25 or younger at the time of diagnosis
of their cancer or plexiform neurofibroma. No procedures will be performed for the sole
purpose of obtaining tissue for this study.
The TMA developed in this study will not be commercialized. The results for individuals whose
tumor specimens are used in the array will not be sent to patients or their treating
physicians.
technology is a recently developed one that allows for evaluating hundreds of tissue samples
simultaneously on the DNA, RNA, and protein levels. The goal is to identify a potential
molecular signature. Cancer drug discovery is currently focused on identifying drugs targeted
at the molecular level. Such drugs would be more selective and specific for proteins and
signaling pathways that are directly involved in the origin of tumors. However, the origin of
cancer among adults differs from that of cancer diagnosed in children. The overall approach
by the pharmaceutical industry in developing drugs is not likely to be aimed at low-incidence
cancers, such as childhood cancers. Thus, the researchers in this study propose to create a
childhood cancer TMA that include specimens from a wide range of solid tumors that present a
poor prognosis for patients. This TMA would in turn be used to identify antibodies and lead
to developing molecularly targeted drugs that would reach clinical trials in adults.
TMAs are created robotically. Small tissue cores are taken from paraffin-embedded tissue
blocks and are implanted into new paraffin blocks. The recipient blocks are then processed to
produce several hundred specimens that can be evaluated on a single glass slide. Specimens
representing 17 distinct kinds of pediatric solid tumors will be used in this study. Also
included will be samples of plexiform neurofibroma-that is, benign growths of nervous and
connective tissues.
Tissue specimens will come from patients who were age 25 or younger at the time of diagnosis
of their cancer or plexiform neurofibroma. No procedures will be performed for the sole
purpose of obtaining tissue for this study.
The TMA developed in this study will not be commercialized. The results for individuals whose
tumor specimens are used in the array will not be sent to patients or their treating
physicians.
Background: Cancer drug discovery is now focused on identifying molecularly targeted drugs
that are more selective and specific for proteins and signaling pathways that are directly
involved in tumorigenesis. This new paradigm alters the approach to clinical drug development
for childhood cancers because the emphasis is on therapeutic targets present in common
epithelially-derived adult cancers, which have a different pathogenesis. The pharmaceutical
industry is unlikely to undertake target discovery programs for low incidence cancers, such
as childhood cancers. Therefore, a more pragmatic approach to the development of molecularly
targeted drugs in children is required.
Objective: Construct a childhood cancer tissue microarrays (TMA) for screening and selecting
the most appropriate molecularly targeted agents for clinical development in childhood
cancers.
Eligibility: Ten to twenty representative specimens (paraffin blocks) for each of 25
histologically distinct pediatric solid tumors or plexiform neurofibromas will be collected.
Design: Using a robotic arrayer, three 0.6 mm cores from each tissue block will be donated
into one of 3 recipient paraffin TMA blocks (CNS tumors, sarcomas, embryonal tumors).
Standard immunohistochemical techniques will be applied to 5 micro m sections from the TMA
block using validated antibodies directed against specific protein targets of interest. If
greater than 8 to 20 tumors from each specific histological type of cancer are positive,
there is a 95% probability that the true proportion of positive specimens exceeds 20%. The
results of the TMA target assessment will guide in the selection of molecularly targeted
drugs for pediatric phase I clinical trials in the POB and Pediatric Phase I/Pilot Consortium
and the selection of candidate tumors for activity testing in phase II clinical trials. If
clinical responses are observed in phase I or II trials in tumor types that express the
target on the TMA, we will return to the original paraffin blocks and perform Laser Capture
Microdissection and produce reverse-phase lysate protein microarrays to assess the activation
state of targeted signaling pathways and investigate the role of the target protein in
tumorigenesis of the responsive childhood cancers.
that are more selective and specific for proteins and signaling pathways that are directly
involved in tumorigenesis. This new paradigm alters the approach to clinical drug development
for childhood cancers because the emphasis is on therapeutic targets present in common
epithelially-derived adult cancers, which have a different pathogenesis. The pharmaceutical
industry is unlikely to undertake target discovery programs for low incidence cancers, such
as childhood cancers. Therefore, a more pragmatic approach to the development of molecularly
targeted drugs in children is required.
Objective: Construct a childhood cancer tissue microarrays (TMA) for screening and selecting
the most appropriate molecularly targeted agents for clinical development in childhood
cancers.
Eligibility: Ten to twenty representative specimens (paraffin blocks) for each of 25
histologically distinct pediatric solid tumors or plexiform neurofibromas will be collected.
Design: Using a robotic arrayer, three 0.6 mm cores from each tissue block will be donated
into one of 3 recipient paraffin TMA blocks (CNS tumors, sarcomas, embryonal tumors).
Standard immunohistochemical techniques will be applied to 5 micro m sections from the TMA
block using validated antibodies directed against specific protein targets of interest. If
greater than 8 to 20 tumors from each specific histological type of cancer are positive,
there is a 95% probability that the true proportion of positive specimens exceeds 20%. The
results of the TMA target assessment will guide in the selection of molecularly targeted
drugs for pediatric phase I clinical trials in the POB and Pediatric Phase I/Pilot Consortium
and the selection of candidate tumors for activity testing in phase II clinical trials. If
clinical responses are observed in phase I or II trials in tumor types that express the
target on the TMA, we will return to the original paraffin blocks and perform Laser Capture
Microdissection and produce reverse-phase lysate protein microarrays to assess the activation
state of targeted signaling pathways and investigate the role of the target protein in
tumorigenesis of the responsive childhood cancers.
- INCLUSION CRITERIA:
Twenty representative formalin-fixed, paraffin-embedded specimens for each of 17
histologically distinct pediatric solid tumors will be collected from the pathology
departments of selected Pediatric Phase I Consortium collaborators.
We found this trial at
1
site
9609 Medical Center Drive
Bethesda, Maryland 20892
Bethesda, Maryland 20892
1-800-422-6237
National Cancer Institute , 9000 Rockville Pike The National Cancer Institute (NCI) is part of...
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