Chromosomal cohesion and separation are essential processes during cell division, ensuring the accurate segregation of sister chromatids. Cohesin, a protein complex, maintains the connection between sister chromatids until their separation during anaphase. The enzyme Separase is responsible for cleaving cohesin, allowing the separation of sister chromatids. Dysregulation of these processes can lead to aneuploidy, a condition characterized by an abnormal number of chromosomes, which is strongly associated with cancer. Aneuploidy is a common feature in many cancers, and abnormalities in chromosomal cohesion and separation contribute to the development of various cancers, including acute myeloid leukemia, myelodysplastic syndrome, and solid tumors. Mutations in the cohesin complex can interfere with chromosomal segregation, genome organization, and gene expression, promoting aneuploidy and malignancy. Understanding the molecular mechanisms of chromosomal cohesion and separation is crucial for developing new therapeutic strategies against cancer. Separase overexpression is linked to aneuploidy and tumorigenesis, and pharmacological inhibition of Separase shows promise as a therapeutic approach. Cohesin mutations also play a role in cancer development, often in conjunction with other genetic mutations. Aneuploidy can have both oncogenic and tumor suppressor effects, and its relationship with chromosomal instability is complex. Targeting aneuploid cancer cells through specific therapies, such as inhibiting Separase or disrupting spindle function, offers new avenues for cancer treatment. The precise regulation of chromosomal cohesion and separation is essential for maintaining genomic stability, and their dysregulation can lead to aneuploidy and cancer. Future research aims to uncover the intricate mechanisms underlying these processes and develop targeted therapies for cancer.Chromosomal cohesion and separation are essential processes during cell division, ensuring the accurate segregation of sister chromatids. Cohesin, a protein complex, maintains the connection between sister chromatids until their separation during anaphase. The enzyme Separase is responsible for cleaving cohesin, allowing the separation of sister chromatids. Dysregulation of these processes can lead to aneuploidy, a condition characterized by an abnormal number of chromosomes, which is strongly associated with cancer. Aneuploidy is a common feature in many cancers, and abnormalities in chromosomal cohesion and separation contribute to the development of various cancers, including acute myeloid leukemia, myelodysplastic syndrome, and solid tumors. Mutations in the cohesin complex can interfere with chromosomal segregation, genome organization, and gene expression, promoting aneuploidy and malignancy. Understanding the molecular mechanisms of chromosomal cohesion and separation is crucial for developing new therapeutic strategies against cancer. Separase overexpression is linked to aneuploidy and tumorigenesis, and pharmacological inhibition of Separase shows promise as a therapeutic approach. Cohesin mutations also play a role in cancer development, often in conjunction with other genetic mutations. Aneuploidy can have both oncogenic and tumor suppressor effects, and its relationship with chromosomal instability is complex. Targeting aneuploid cancer cells through specific therapies, such as inhibiting Separase or disrupting spindle function, offers new avenues for cancer treatment. The precise regulation of chromosomal cohesion and separation is essential for maintaining genomic stability, and their dysregulation can lead to aneuploidy and cancer. Future research aims to uncover the intricate mechanisms underlying these processes and develop targeted therapies for cancer.