Defining the Value of a Comparative Approach to Cancer Drug Development

LeBlanc, Amy K.; Mazcko, Christina; Khanna, Chand

doi:10.1158/1078-0432.ccr-15-2347

Cited by 63 publications

(68 citation statements)

References 57 publications

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“…A summary of this conference has recently been reported (51). These offer unique opportunities for drug and chemo-radiotherapy development (52). Canine tumors are genetically diverse, grow relatively slowly, exhibit spatio-temporal heterogeneity and diversity, are amenable to imaging studies, and can help assess cost-effective treatment choices (53).…”

Section: Focus Areas: Preclinical Radiobiological Assaysmentioning

confidence: 99%

Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials

Coleman

Higgins

Brown

et al. 2016

Clinical Cancer Research

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There is an urgent need to improve reproducibility and translatability of preclinical data in order to fully exploit opportunities for molecular therapeutics involving radiation and radio-chemotherapy. For in vitro the clonogenic assay remains the current state-of-the-art of preclinical assays, while newer moderate- and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action and address immune modulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies, for example, regrowth delay measures bulk tumor killing while local tumor control assesses effects on CSC. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radio-chemotherapy for most tumors. Radiation models are compatible with, but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapy enhancer may be different than its interaction with radiation and/or radio-chemotherapy. This provides an opportunity to expand the use of molecular-targeted agents.

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Section: Focus Areas: Preclinical Radiobiological Assaysmentioning

confidence: 99%

Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials

Coleman

Higgins

Brown

et al. 2016

Clinical Cancer Research

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“…This Consortium's overarching mission is to improve the quality and forward progress of brain tumor research by leveraging the study of spontaneous brain tumors in pet dogs, and is an extension of the National Cancer Institute's Comparative Oncology Program, which has led the field of comparative oncology research for over a decade. There is substantial evidence that the study of naturally occurring cancers in dogs can meaningfully contribute to many fields of cancer research, including neurooncology, as tumor‐bearing pet dogs are a disease model that complements knowledge gained in mouse models and through human clinical research . Within the Comparative Brain Tumor Consortium, five distinct working groups were formed to facilitate cross‐discipline communications and generate new knowledge in the following areas: tumor biology, clinical trials, drug development, pathology and molecular markers, and patient outcomes …”

Section: Introductionmentioning

confidence: 99%

Consensus recommendations on standardized magnetic resonance imaging protocols for multicenter canine brain tumor clinical trials

Packer

Rossmeisl

Kent

et al. 2018

Vet Radiology Ultrasound

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The National Cancer Institute Comparative Brain Tumor Consortium, Patient Outcomes Working Group, propose a consensus document in support of standardized magnetic resonance imaging protocols for canine brain tumor clinical trials. The intent of this manuscript is to address the widely acknowledged need to ensure canine brain tumor imaging protocols are relevant and have sufficient equivalency to translate to human studies such that: (1) multi-institutional studies can be performed with minimal inter-institutional variation, and (2) imaging protocols are consistent with human consensus recommendations to permit reliable translation of imaging data to human clinical trials. Consensus recommendations include pre- and postcontrast three-dimensional T1-weighted images, T2-weighted turbo spin echo in all three planes, T2*-weighted gradient recalled echo, T2-weighted fluid attenuated inversion recovery, and diffusion weighted imaging/diffusion tensor imaging in transverse plane; field of view of ≤150 mm; slice thickness of ≤2 mm, matrix ≥ 256 for two-dimensional images, and 150 or 256 for three-dimensional images.

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“…There are many advantages of such a model and the most important of them include the following: (a) spontaneous occurrence of tumors in immunocompetent individuals; (b) naturally developing treatment resistance of the cancer cells; (c) spontaneous recurrence and metastasis; (d) possibility of canine patients monitoring for hematologic and biochemical toxicity via routine clinical pathology, and sophisticated monitoring like in human medicine; (e) ability to notice the impact of supportive care (e.g., antiemetics, antidiarrheals, antibiotics, etc.) on the course of a therapy; (f) occurrence of heterogeneity within the cancer [7]. All of the above advantages encourage scientists to design research involving dogs and the results obtained this way become a valuable source of medical information.…”

Section: Comparative Oncology-canine Models In Cancer Biology and Thementioning

confidence: 99%

The Role of Bcl-xL Protein Research in Veterinary Oncology

Pawlak

Henklewska

2020

IJMS

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Due to their significant impact on human and animal health, cancer diseases are an area of considerable concern for both human and veterinary medicine. Research on the cancer pathogenesis in companion animals, such as dogs, allows not only for improving canine cancer treatment, but also for translating the results into human oncology. Disruption of apoptosis in tumor-transformed cells is a well-known mechanism leading to the development of cancer. One of the main factors involved in this process are proteins belonging to the B-cell lymphoma 2 (Bcl-2) family, and the imbalance between pro-apoptotic and anti-apoptotic members of this family contributes to the development of cancer. Studies on the function of these proteins, including B-cell lymphoma-extra large (Bcl-xL), have also been intensively conducted in companion animals. The Bcl-xL gene was sequenced and found to share over 99% homology with the human protein. Research showed that the Bcl-2 family plays the same role in human and canine cells, and data from studies in dogs are fully translatable to other species, including humans. The role of this protein family in cancer development was also confirmed. The article presents the current state of knowledge on the importance of the Bcl-xL protein in veterinary oncology.

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Defining the Value of a Comparative Approach to Cancer Drug Development

Cited by 63 publications

References 57 publications

Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials

Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials

Consensus recommendations on standardized magnetic resonance imaging protocols for multicenter canine brain tumor clinical trials

The Role of Bcl-xL Protein Research in Veterinary Oncology

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