Abstract B40: A new approach to optimizing the drug discovery and development pipeline for breast cancer

Abstract

Abstract The current pipeline of drug discovery and development takes a long time, and is very expensive. One of the major obstacles in this process is the high rate of clinical attrition, with less than 14% of oncology drugs that enter human clinical testing getting approved and reaching the market. A primary reason that few drugs make it through human clinical trials is that the current approaches used in preclinical tests (cells, mice, and rats) provide a poor predictive response for therapeutic efficacy and toxicity. There is a strong need for innovative approaches that can overcome the limitations of the conventional models. Conducting clinical trials in pet dogs with spontaneous mammary tumors is here suggested as an alternative method of investigating new drugs for human breast cancer, due to the large number of similarities between human and dog biology. Several factors make pet dogs with mammary cancer a promising avenue for translational studies of human breast cancer. 1) The canine genome has strong similarities with the human genome, 2) Human and dog genes present a parallel evolution for metabolism and cancer, 3) Mammary tumors in dogs occur spontaneously and display a similar complexity and heterogeneity as in humans, 4) Human and dog mammary cancers share similar alterations in the signaling pathways and expression of molecular markers, 5) Aging and obesity are associated with higher risk for development of mammary cancer in both dogs and humans, 6) In contrast to rodents in a laboratory, pet dogs are exposed to the same environment as humans, including ambient toxins, and are a highly heterogeneous population, 7) The duration needed to evaluate the treatment efficacy is shorter in dogs than humans; 1-2 years for dogs instead of 5-10 years for humans. Importantly, like humans, dogs die due to metastases, and new treatments are required to control metastatic disease in both species. We propose the implementation of a new system for oncologic drug evaluation for breast cancer through performing clinical trials at veterinary hospitals in dog patients with mammary tumors. This phases of implementation include: 1) Establishing international clinical trial programs in areas where canine mammary cancer has a high incidence (e.g. Brazil). For this, we are building standardized electronic data formats, based on CDISC (Clinical Data Interchange Standards Consortium) standards, and promoting relationships between the hospitals and US-based pharma companies, and developing a platform to facilitate the sharing of data among the participating organizations, through a bilingual English/Portuguese interface. 2) Conducting a low-cost, proof-of-concept deployment of the platform, through veterinary clinical trials with a generic drug that has already been shown to be effective in human breast cancer. 3) Approaching pharma companies, using the evidence gathered during phase 2, to propose leveraging this platform and its network, to conduct early clinical trials of drugs in canine patients. This innovative approach can help to optimize the drug development pipeline for breast cancer, speeding the discovery of new drugs. Furthermore, performing clinical trials in dogs with spontaneous cancer could be a more ethical and socially acceptable research approach than in vivo laboratory work, since the drugs would also be directly benefiting dogs as much as patients. Strategies of combining several drug targets can easily be carried out in dogs, providing results about combinations that can minimize drug resistance and recurrence. In addition, the existence of extremely aggressive tumors in dogs, such as triple negative and inflammatory tumors, that do not have a target therapy, makes dogs a remarkable hope in the discovery of new drugs for these types of human breast cancer. Citation Format: Isabelle Tancioni, Jamie Alexandre. A new approach to optimizing the drug discovery and development pipeline for breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr B40.