Evolution of Organoids in Oncology

*Allen Thayakumar Basanthakumar, Janitha Chandrasekhar Darlybai and Jyothsna Ganesh*

## **Abstract**

An organoid is an *in-vitro* platform that recreates 3D multicellular aggerates to form tissues that fabricate the human cellular environment in the lab and imitate the functionalities of the specific organ or disease. Organoids effectively overcomes the gaps in research between 2D cell line and *in-vivo* models. For organoid development, both pluripotent stem cells and embryonic stem cells can be utilized, and recently Patient-Derived Organoids (PDO) was developed that overcome the limitations caused by using other cell lines. With the development of many advanced technologies in the field of research, the organoid evolution also progressed slowly into the development of patient-specific organ structures. Since tumor organoids were heterogeneous as well as patient-specific, it has many advantages that aid cancer therapy effectively. Apart from cancer treatment, organoids have a variety of applications in cancer research, the study of tissue-specific models, and also in the analysis of the relationship between tissue-specific cancer with various pathogens. Thus, the development of organoids in an effective way can pave the way for various biomedical applications. This chapter focuses on the trends in the journey of organoid research and the latest technologies developed specifically for organoids.

**Keywords:** organoid, 3D tissues, cancer research, cancer therapy

## **1. Introduction**

Cancer is a heterogeneous disease that is caused by the progress of somatic mutations in normal cells [1]. Based on studies it was confirmed that continuous exposure to physical agents such as X-rays, gamma rays, UV rays, and genotoxic factors may end up in the progress of cancer cells from normal cells [2]. Carcinogenesis is a complex process that involves various pathways which need to be studied to understand the response and treatment method required for targeted therapy which is a complicated mechanism [3].

The development of drugs by using medicinal plants as bio source has also been studied extensively in various research [4]. It is essential to understand the biological interaction among immune cells among tumor immune microenvironment, stroma, and tumor for the success of cancer clinical treatments [5]. The overall cancer therapy may vary with multiple metastatic sites which in turn depend on the tumor

#### **Figure 1.**

*Flowchart of use of normal organoids in making tumor organoids and utilization of tumor organoids in a biobank and its applications [13–18].*

heterogeneity [6]. The major biological complexities make the treatment methods difficult which in turn varies with the metastatic sites among individual patients [7]. The microenvironment of tumor cells includes normal stroma, malignant cells, and immune response based on every individual [8]. The durability and patient-to-patient response extremely varies based on each patient and hence very difficult to predict the consequences [9].

An organoid is an emerging technology with various applications in biomedical applications such as biobanking, disease modeling, regenerative medicine, and precision medicine [10]. An organoid is a technology used to fabricate 3D tissues in the laboratory that resembles parent tissue in function and structure and hence bridges the gap between 2D *in-vitro* and *in-vivo* models so that they can be utilized effectively in cancer research [11]. Though many cancer treatments were available the tumor heterogeneity limits the treatment as the drug sensitivity, drug invasion ability, growth rate of tumor changes based on individuals [12]. In the current review, the history and progressions in the developments of organoids were elaborated accompanied by their applications in cancer treatment along with their limits and steps required to overcome the limitations so that the organoid technology can be implemented efficiently in future research. Overview showed in **Figure 1**.
