{Reference Type}: Journal Article {Title}: Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy. {Author}: Uinarni H;Oghenemaro EF;Menon SV;Hjazi A;Ibrahim FM;Kaur M;Zafarjonovna AZ;Deorari M;Jabir MS;Zwamel AH; {Journal}: Cell Biochem Biophys {Volume}: 0 {Issue}: 0 {Year}: 2024 Jun 25 {Factor}: 2.989 {DOI}: 10.1007/s12013-024-01367-w {Abstract}: Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.