There is a pertinent need to develop prognostic biomarkers for practicing predictive, preventive and personalized medicine (PPPM) in colorectal cancer metastasis. The analysis of isoform expression data governed by alternative splicing provides a high-resolution picture of mRNAs in a defined condition. This information would not be available by studying gene expression changes alone. Hence, we utilized our prior data from an exon microarray and found ADAM12 and MUC4 to be strong biomarker candidates based on their alternative splicing scores and pattern. In this study, we characterized their isoform expression in a cell line model of metastatic colorectal cancer (SW480 & SW620). These two genes were found to be good prognostic indicators in two cohorts from The Cancer Genome Atlas database. We studied their exon structure using sequence information in the NCBI and ENSEMBL genome databases to amplify and validate six isoforms each for the ADAM12 and MUC4 genes. The differential expression of these isoforms was observed between normal, primary and metastatic colorectal cancer cell lines. RNA-Seq analysis further proved the differential expression of the gene isoforms. The isoforms of MUC4 and ADAM12 were found to change expression levels in response to 5-Fluorouracil (5-FU) treatment in a dose-, time- and cell line-dependent manner. Furthermore, we successfully detected the protein isoforms of ADAM12 and MUC4 in cell lysates, reflecting the differential expression at the protein level. The change in the mRNA and protein expression of MUC4 and ADAM12 in primary and metastatic cells and in response to 5-FU qualifies them to be studied as potential biomarkers. This comprehensive study underscores the importance of studying alternatively spliced isoforms and their potential use as prognostic and/or predictive biomarkers in the PPPM approach towards cancer.

Advanced therapeutic medicinal products (ATMPs) such as gene, somatic cell, and tissue-engineered therapies have transformed modern healthcare by treating previously unmanageable genetic, oncologic, and degenerative diseases. Although regulatory and developmental frameworks for ATMPs are established in the United States, Europe, and China, limited data exist on their implementation in emerging markets such as Saudi Arabia. This review provides the first comprehensive analysis of ATMP regulation and development in Saudi Arabia while offering novel insights into the nation's evolving clinical trial landscape, regulatory infrastructure, and biomanufacturing capabilities. We conducted a narrative review of the Saudi Food and Drug Authority (SFDA) guidelines, peer-reviewed literature, and clinical trial registrations from 2010 to 2025. As of 2025, the SFDA has approved eight ATMPs, including chimeric antigen receptor T-cell therapy (CAR-T) therapies, adeno-associated virus (AAV) based vectors, and clustered regularly interspaced short palindromic repeats (CRISPR) based therapies, reflecting growing regulatory maturity and international alignment. Clinical trial activity continues to expand, with a concentration in oncology, hematology, and rare genetic diseases. National research institutions such as the King Faisal Specialist Hospital and Research Centre (KFSHRC) and King Abdullah International Medical Research Center (KAIMARC) have pioneered advances in CAR-T manufacturing, while biobanking initiatives are driving translational research. Despite ongoing challenges in workforce capacity, good manufacturing practice (GMP) infrastructure, and reimbursement mechanisms, Saudi Arabia is positioned to become a regional leader in advanced therapies through continued regulatory innovation, local manufacturing, and international collaboration.