Application of 3D organoid for early diagnosis prognosis, and therapeutic approaches of oral cancer
Application of 3D organoid for early diagnosis prognosis, and therapeutic approaches of oral cancer
Ensieh Sagheb Sadeghi,1,*Haniye Tahamtan Nezhad,2Elnaz Montazami Vazifeh Doost,3
1. Department of Biology,Neyshabur Branch,Islamic Azad University, Neyshabur Iran 2. Department of Biology,Mashhad Branch,Islamic Azad University, Mashhad Iran 3. Department of Biology,Mashhad Branch,Islamic Azad University, Mashhad Iran
Introduction: Oral cancers are the sixteenth most common cancer worldwide, with 90% comprising oral squamous cell carcinoma (OSCC), affecting more than 300,000 individuals annually. Alcohol drinking, tobacco consumption, and human papillomavirus (HPV) infection are the main high-risk factors for oral cancers. Conventional treatments include chemotherapy, radiotherapy, and surgery that have not significantly reduced the high morbidity rate. Late diagnosis in the end stage of OSCC and the absence of a definitive biomarker for early diagnosis through clinical examination and histopathological analysis remain poor prognoses.
Methods: Recent studies revealed that biological fluids, including blood, urine, saliva, etc., have the potential for early diagnosis. Some benefits of the biofluid assessment include accessible sample collection, noninvasive sampling, and economical and valid outcomes. In addition to the late diagnosis, selecting appropriate individual therapeutic approaches is another challenge in oral cancer patient management. Since oral cancers, specifically OSCCs, are heterogenous, we need reliable individualized therapy that predicts clinical responses. Personalized medicine or precision medicine has opened a new avenue for therapeutic approaches based on the unique genetic profiles of individuals following the variation. This genomic signature causes different responses to the therapy to apply appropriate drugs with minimum side effects. The advanced technology of high-throughput analysis, next-generation sequencing (NGS), microarray, transcriptomics, and proteomics promote the knowledge of specific variants that can affect therapeutic approaches.
Results: Organoid technology provides this opportunity for preclinical prediction and response to treatment before being applied to patients. In recent years, three-dimensional (3D) culture technologies known as "mini-organ" have been rapidly developed, which is a three-dimensional (3D) structure that mimics morphological, functional, and genetic characteristics of the target tissue of origin in a specific scaffold. Tumor organoids derived from patients (PDO) can be applied for drug screening and biomarker detection. Organoid technology is suitable for studying heterogeneous tumors such as oral cancers. Human organoid models are established from two types of stem cells, including pluripotent stem cells (PSCs) and adult stem cells (ASC), with the self-renewal ability and potential for multi-differentiation. Then, 3D organoids can be applied for regenerative medicine, tissue engineering, and disease modelling. Single-cell high throughput analysis by circulating tumor cells (CTCs) and genetic manipulation by gene editing technology are the other critical applications of organoids for oral cancer.
Conclusion: Organoids allow us this opportunity to evaluate the pathogenesis of cancer, tumor cell behaviour in a mimic environment, and drug screening in a living biobank due to personalized medicine.