**2. The use of humanized models for cancer treatment**

In the initial phase, the genetically engineered mouse models (GEMMs) provided a better appreciation for cancer treatment [19]. But later for practical applications,

*Evolution of Organoids in Oncology DOI: http://dx.doi.org/10.5772/intechopen.104251*

GEMMs technologies were identified to be expensive, laborious, and fetch up into complications when transformed into therapeutic applications [20]. One of the methods of generation of organoids is the utilization of Pluripotent stem cells (iPSCs), but the tissues generated from these embryonic stem cells were found to be phenotypically unstable and hence have the same limitations [21]. Later, Patient-derived xenografts (PDXs) were contemplated as a better replacement to conquer these constraints since, in this technology, models were provoked from an enormous pool of patients [22]. Unfortunately, these techniques also ended up in complications as the cancer cell lines generated *in-vitro* were genetically unstable and were devoid of the cellular microenvironment of tumor cells *in-vivo* and in most cases these cell lines ended up in unmatched cell lines from normal tissue which was considered as control cell lines [23].

Patient-derived tumor xenografts (PDTXs) is the recently available technology in cancer research that can maintain genomic stability and tumor heterogeneity but the major drawback of PDXs is that it is expensive and time-consuming and hence treatment gets delayed [13]. Later PDTXs technologies were upgraded by transplanting these cell lines into mouse models, but PDTXs failed to replicate the human-specific immune systems and were also ended up as a laborious and expensive process [14]. The clinical response of cancer treatment depends on the clinical model used for the study [24].

## **3. Organoids and their types**

The unique way to improve cancer research has emerged with the help of organoid technology that accompanies tumor heterogeneity at low cost and with less time [25]. Cancer organoids serve as an effective tool to understand the interaction between tumor environment and genetic alterations [15]. The organoids derived from postnatal or adult tissue were termed ASC-derived organoids. In the case of ESCs and iPSCs derived organoids, the generation of organoids takes place from all three germ layers. For all these types of organoids, the growth of cells was carried out by using a series of differentiation protocols by utilizing growth factors and inhibitors in the process of organogenesis [11]. Recently many patient-derived organoids (PDTOs) have been developed that include liver, prostate cancer, and pancreatic cancer organoids [26]. A snapshot of types is shown in **Figure 2**.

To make more clarity to organoids, CRISPER gene-editing technology is being implemented to organoid to convert normal organoids into tumor organoids [25]. Upon various research, mutations have been induced in normal organoids like intestinal organoids [40], colon organoids [41], pancreatic organoids [42] to make them into tumor organoids that paves the way for flexible *in-vitro* cancer models. Apart from carcinogenesis, cancer organoids were also being implemented to study cancer metastasis which is the process of spreading cancer cells to other parts of the body [43]. Cancer organoids have also extended their applications in drug screening since PDTOs can be utilized to study gene expression, pathology, and tissue-specific genetic alterations [44]. Few researchers have used cancer organoids to generate tumor-reactive T cells that can be used in immunotherapy [45].

The brief details about various types of organoids have been discussed below:

### **3.1 Intestinal organoids**

The pluripotent stem cells (iPSCs) were used to derive intestinal organoids that contain both mesenchymal and epithelial cells [27]. The basic intestinal crypt cells

**Figure 2.** *Development of 3D organoids culture [27–39].*

were allowed to grow in an appropriate medium containing a matrix that tends to organize into 3D epithelial cells that contain both physical and genetic resemblance of their parent organ [28].
