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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - ZEBRAONCOFISH (Zebrafish avatar as a real-time in vivo platform for personalized cancer therapeutics)

Teaser

Cancer is a leading cause of morbidity and mortality with approx. 35 million people affected by this disease and more than 8 million deaths per year. A major difficulty found in effective cancer treatment is the complexity of the biological mechanism underlying cancer onset...

Summary

Cancer is a leading cause of morbidity and mortality with approx. 35 million people affected by this disease and more than 8 million deaths per year. A major difficulty found in effective cancer treatment is the complexity of the biological mechanism underlying cancer onset and disease progression. This is because the genetic makeup and metabolic profile of each individual patient influence the effect of anticancer drugs. As such, different people respond differently to the same therapy.
Therefore, the solution we propose in the ZEBRAONCOFISH project is the use of zebrafish avatars as an in vivo platform to guide therapeutic decisions in actionable cancer patient-directed interventions. These avatars will be created by xenotransplantation (interspecies transplant) of human cancer cell lines/ tumor samples in zebrafish. The chance to carry out a dynamic display of the cancerous process in vivo will offer the unique opportunity to understand the subjacent cancer biology and design tailor-made treatments for each patient.
The obvious question is: if zebrafish can offer such clear advantages, why are they not used currently in a clinical routine to support the selection of the best cancer treatment? This is because there are still some barriers preventing this to happen, which if not been so important for drug discovery in the Pharma industry where zebrafish models are increasingly gaging popularity (the cost and time efficiency of zebrafish models compared with mammalian models in pre-clinical drug testing is far enough to justify their increasing use), they are important barriers when it comes to actionable patient-directed interventions. These barriers are the following:
- Even costs are an 80-85% lower than mouse models, they are still high should zebrafish avatars have to be afforded by the patients, the private insurance companies and even worst for the National Health systems. These costs are a result of the large number of fish required for screening the most used chemotherapy drugs approved for clinical use with statistical relevance. Currently the use of zebrafish avatars in selection of the best drug combination for a given patient requires a minimum of 180 fish: at least 20 combinations of chemotherapy drugs must be analyzed and each combination must be tested with at least 3 fish and in triplicate (to avoid confounding factors).
- In spite of the possibility to perform high-throughput analysis of drug combinations efficiency (using 96 well micro-plate based assays), the process of xenotransplantation still requires manual injection of the human cells, which can be a time-consuming technical hurdle. This is an important barrier, special for the amount of fish required in the study (>180) and as a result the time for delivering the results the patients is around 6 weeks, which if compared with the 3-4 months required to observe drug effects in mouse models is very short, but it is still a long period for actionable patient-directed interventions.
In the ZEBRAONCOFISH project we seek overcoming the aforementioned barriers preventing the use of zebrafish avatars in patient-directed interventions. In this way, we want becoming the first company worldwide delivering on the advantages of their use in personalized medicine to cancer patients. Our approach to overcome the two barriers explained in the previous page goes through the following objectives:
• OBJECTIVE 1: To reduce the price of the analysis, a reasonable price for a routine-use analysis in clinic.
• OBJECTIVE 2: To reduce the time required to deliver the results of the analysis to the patients from 6 weeks to a maximum of 1 week.

Work performed

The specific contributions towards the objectives per Work Package have been described below:
• WP1 for Project Management: During these 2 years of the project, the activities in the WP have been carried out efficiently. This WP has thereby laid a solid basis upon which to execute all activities in the other WPs.
• WP2 for Process standardization & automation for xenotransplantation and analysis: During these months, the standardization of the process as well as the automation are defined accordingly to the tumor type studied. This WP is becoming the most complex part of the project. Concerning certification, an assessment of certification has been conducted.
• WP3 is devoted to Clinical Study for Technology validation & development of the phenotype-molecules library: This WP of the project was carried out during the last months. The provision of biopsies is not being adequate inasmuch as the frequency of collection is not being than we previously planned. The reason why is not easy the collection of the surplus, should always take into account no compromising the diagnosis.
• WP4 for Exploitation, IP Strategy & Commercialization Activities: The update of the Commercialization Plan is being carried out on stakeholders and events basis. In a reference to IP, we evaluated which is the best strategy to follow.
• WP5 Dissemination & visibility actions: Besides the management of the project activities, stakeholder involvement are described in more detail on the following sections.

Final results

The expected impacts will be achieved pursuing the ZEBRAONCOFISH objectives and its approach. Through the ZEBRAONCOFISH project, we aim to position our company as leader in the personalized medicine market and more specifically in the Companion Diagnostic (CDx) segment.
At the completion of the ZEBRAONCOFISH project, we will envisage to target first the European market and may reach the US market in a near future (the fourth selling year). In the specific case of ZEBRAONCOFISH, we targeted two different clients: clinical sector (Hospitals and clinics) and companies (Biotech and Pharma).
The social benefits of our project are unquestionable, as it contributes to reduce the high mortality of cancer and it s one of the most important points of convergence in developed modern societies. Considering the economic burden of cancer amounts for more than €126 billion, it is obvious that it is a major concern for the sustainability of the healthcare systems. One via for cost’s reductions will be achieved by reduction of costs of ineffective therapies. It is very difficult to provide an accurate estimation of the costs reductions achievable at this stage, but we consider realistic these costs can be 1% of the total, if ZEBRAONCOFISH is implemented globally, representing ~€100M yearly for the healthcare systems worldwide. Besides government investment, is crucial to create a strong environment in which research can be conducted to improve the cancer outcomes.
This will not only benefits patients and their families, it will also have a high impact in a population that lives longer and healthier lives, saving incredible amount of money to society, health system and insurance companies.
The economic impact for our company will be very high. At the end of this project we will be able to sell services whose turnover will represent 78% of the total turnover of our company.

Website & more info

More info: http://zebraoncofish.com/.