The chromosomal theory of cancer is a fundamental concept in cancer biology that suggests cancer is caused by genetic changes, particularly alterations in the structure or number of chromosomes in cells. These changes can lead to uncontrolled cell growth, a hallmark of cancer.[1]
Historical background[edit]
The theory originated from the work of Theodor Boveri, a German biologist, in the early 20th century. Boveri's studies on sea urchin eggs provided early evidence that abnormal chromosome numbers could lead to developmental defects, leading him to propose a connection between chromosomal abnormalities and cancer.[2]
Further research by scientists such as David Hungerford and Peter Nowell in the 1960s identified specific chromosomal abnormalities in cancer cells, such as the Philadelphia chromosome in chronic myeloid leukemia, providing more support for the chromosomal theory of cancer.[3]
Key concepts[edit]
Normal cells have a precise and stable number of chromosomes, which is crucial for proper cell function and division. Chromosomes contain genes that control cell growth, differentiation, and other cellular processes.[4]
Cancer cells often exhibit chromosomal abnormalities, including chromosomal rearrangements (such as translocations), deletions, and duplications. These abnormalities can disrupt the normal function of genes involved in cell cycle regulation, leading to uncontrolled cell growth and tumor formation.[4]
Mechanisms[edit]
Chromosomal abnormalities can contribute to cancer development through several mechanisms,
Activation of oncogenes[edit]
Chromosomal rearrangements can lead to the fusion of genes, creating oncogenes that promote cell growth and division uncontrollably.
Inactivation of tumor suppressor genes[edit]
Chromosomal deletions or mutations can lead to the loss of tumor suppressor genes, which normally inhibit cell growth. Loss of these genes can further promote uncontrolled cell growth and tumor formation.
Genomic instability[edit]
Chromosomal abnormalities can cause genomic instability, leading to additional mutations and genetic changes that contribute to cancer progression.[5][6]
Experimental evidence[edit]
Experimental studies using cell lines, animal models, and human cancer samples have provided strong evidence supporting the chromosomal theory of cancer. These studies have demonstrated that chromosomal abnormalities can drive tumorigenesis and are often associated with specific types of cancer.[7]
Clinical relevance[edit]
Chromosomal analysis, such as karyotyping and fluorescence in situ hybridization (FISH), is commonly used in cancer diagnosis and prognosis to detect chromosomal abnormalities in cancer cells.[8][9]
Targeted therapies, such as imatinib for chronic myeloid leukemia[10] and trastuzumab for HER2-positive breast cancer,[11] have been developed based on the specific chromosomal abnormalities associated with these cancers.
Current research and future directions[edit]
Current research in cancer genetics is focused on further understanding the role of chromosomal abnormalities in cancer development and progression. Advances in technology, such as next-generation sequencing, are enabling researchers to study chromosomal abnormalities in cancer cells with greater detail and precision.[12]
Future directions include the development of new targeted therapies and personalized medicine approaches based on the specific chromosomal abnormalities present in individual patients' tumors.
See also[edit]
References[edit]
- ^ Duesberg, Peter; Li, Ruhong; Fabarius, Alice; Hehlmann, Ruediger (2005). "The chromosomal basis of cancer". Cellular Oncology: The Official Journal of the International Society for Cellular Oncology. 27 (5–6): 293–318. doi:10.1155/2005/951598. ISSN 1570-5870. PMC 4615177. PMID 16373963.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ McKusick, V. A. (December 1985). "Marcella O'Grady Boveri (1865-1950) and the chromosome theory of cancer". Journal of Medical Genetics. 22 (6): 431–440. doi:10.1136/jmg.22.6.431. ISSN 0022-2593. PMC 1049502. PMID 3908684.
- ^ Nowell, Peter C. (2007-08-01). "Discovery of the Philadelphia chromosome: a personal perspective". Journal of Clinical Investigation. 117 (8): 2033–2035. doi:10.1172/JCI31771. ISSN 0021-9738. PMC 1934591. PMID 17671636.
- ^ a b "How chromosome imbalances can drive cancer". Broad Institute. 2023-06-28. Retrieved 2024-04-01.
- ^ "Chromosome Abnormalities and Cancer Cytogenetics | Learn Science at Scitable". www.nature.com. Retrieved 2024-04-01.
- ^ Thompson, Sarah L.; Bakhoum, Samuel F.; Compton, Duane A. (2010-03-23). "Mechanisms of Chromosomal Instability". Current Biology. 20 (6): R285–R295. Bibcode:2010CBio...20.R285T. doi:10.1016/j.cub.2010.01.034. ISSN 0960-9822. PMC 3781365. PMID 20334839.
- ^ "An alternative theory on cancer". medicalxpress.com. Retrieved 2024-04-01.
- ^ Shakoori, Abdul Rauf (2017-02-10). "Fluorescence in Situ Hybridization (FISH) and Its Applications". Chromosome Structure and Aberrations. pp. 343–367. doi:10.1007/978-81-322-3673-3_16. ISBN 978-81-322-3671-9. PMC 7122835.
- ^ "Fluorescence In Situ Hybridization (FISH)". www.genome.gov. Retrieved 2024-04-01.
- ^ Sacha, Tomasz (2014-01-02). "Imatinib in Chronic Myeloid Leukemia: an Overview". Mediterranean Journal of Hematology and Infectious Diseases. 6 (1): e2014007. doi:10.4084/MJHID.2014.007. ISSN 2035-3006. PMC 3894842. PMID 24455116.
- ^ Gajria, Devika; Chandarlapaty, Sarat (February 2011). "HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies". Expert Review of Anticancer Therapy. 11 (2): 263–275. doi:10.1586/era.10.226. ISSN 1473-7140. PMC 3092522. PMID 21342044.
- ^ "Abnormal Chromosomes: The Past, Present, and Future of Cancer Cytogenetics | Wiley". Wiley.com. Retrieved 2024-04-01.
- ^ "How Chromosome Imbalances Can Drive Cancer | Harvard Medical School". hms.harvard.edu. 2023-07-06. Retrieved 2024-04-01.
- ^ Fröhling, Stefan; Döhner, Hartmut (2008-08-14). "Chromosomal abnormalities in cancer". The New England Journal of Medicine. 359 (7): 722–734. doi:10.1056/NEJMra0803109. ISSN 1533-4406. PMID 18703475.
