Research Article: Chorioallantoic urothelial tumor avatar. A clinical tool for phenotype-based therapy 1

Date Published: February 10, 2020

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Marina Vian Ossick, Karen Linares Ferrari, Igor Nunes-Silva, Fernandes Denardi, Leonardo Oliveira Reis.


In the muscle invasive bladder cancer (MIBC) standard of care treatment only patients presenting a major pathological tumor response are more likely to show the established modest 5% absolute survival benefit at 5 years after cisplatin-based neoadjuvant chemotherapy (NAC). To overcome the drawbacks of a blind NAC (i.e. late cystectomy with unnecessary NAC adverse events) with potential to survival improvements, preclinical models of urothelial carcinoma have arisen in this generation as a way to pre-determine drug resistance even before therapy is targeted. The implantation of tumor specimens in the chorioallantoic membrane (MCA) of the chicken embryo results in a high-efficiency graft, thus allowing large-scale studies of patient-derived “tumor avatar”. This article discusses a novel approach that exploits cancer multidrug resistance to provide personalized phenotype-based therapy utilizing the MIBC NAC dilemma.

Partial Text

Bladder cancer corresponds to over 90% of all urothelial tumors and positions 7th and 17th in the tumors ranking, respectively, between men and women. It affects approximately 110.000 men and 70.000 women each year in the world. In Brazil, there were 9.670 new cases in 2016 (7.200 in men and 2.470 in women). In the United States, the American Cancer Association estimates 79.030 new bladder cancer cases diagnosed in 20171 , 2 .

In 1874, Willian Roberts and John Tyndall observed the growth of bacteria in the liquid medium and reported the inhibitory effects of penicillin, thus observing inhibition of the growth of colonies on the agar plate. In 1940, Heatley suggested the use of filter paper discs that contained antimicrobial solutions and Mohs introduced a “radial disc method”. It was the first proposal of evaluation of phenotype of the response of microorganisms to antibiotic treatment, comparing the radius of the proliferation of colonies. After several studies and findings, the World Health Organization (WHO) released a report on the methodology in 1975 and this method is the standard of the International Committee of Clinical Laboratory Standards13 .

The chorioallantoic membrane (CAM) assay has been used as a rapid low cost reproducible method to test potential antitumor drugs in vivo . This assay has been widely used to study angiogenesis and has also been successfully developed in a tumor xenograft model, including tumors of the pancreas, melanoma, and osteosarcoma, due to the total non-development of the lymphoid system of the embryo, limiting tissue rejection, opening opportunities for new techniques and protocols.

Seeing the need for more individualized treatment, we fall within the scope of the tumor phenotype, since the same type of tumor can become resistant to different types of drugs, once it has potential to adapt to its host defense mechanisms and characteristics.

Like the established antibiogram as the main tool in the treatment of urinary tract infection that anticipates the bacteria antibiotic sensitivity/susceptibility, can we define and anticipate the best treatment (”tumor chemogram”) for every individual bladder cancer patient using an ultra-fast treatment response phenotype platform such as chorioallantoic tumor avatar?

The efficiency optimization of the immediate and rescue sowing (in 24 and 48h using frozen tissue -80oC) as strategy in cases of failure of the primary sowing, the further understanding of the neoplastic tissue stability and characteristics maintenance (genomic, proteomic, metabolomic and phenotypic) in the proposed platform as well as the definition of this approach impact in the implementation of individualized treatment, its costs and results (oncological and functional) in patients with urothelial carcinoma are underway.