Cancer Doesn't
Play Fair
Cancer will try anything to win, including enlisting the help of IB6 (integrin beta‑6).1
Find out why that matters
When it comes to cancer, Where is IB6 found?
IB6 is an integrin that is highly expressed in a range of solid tumors1‑10
Integrins, including IB6, comprise a family of protein heterodimers that mediate signaling between cells and the extracellular matrix. They are involved in a variety of normal cellular activities, including proliferation, adhesion, motility, and angiogenesis. IB6 is nearly undetectable in most adult epithelial tissue but is highly expressed in many tumor types.1,11‑13
Incidence of tumor samples that are positive for IB6 expression across tumor types
How could IB6 be giving cancer an unfair advantage?
IB6 plays an important role in promoting key oncogenic processes1,13‑17
Migration
Upregulation of IB6 is associated with epithelial-to-mesenchymal transition, a phenotypic shift during which cell-to-cell adherence is lost and the ability of cells to migrate is enhanced.1,14
Invasion
Within an IB6-expressing tumor, IB6 tends to be most highly expressed at the leading tumor edge, indicating a possible role in helping tumors penetrate surrounding tissue.13,15,16
Proliferation
In preclinical studies, expression of IB6 increased tumor cell proliferation while silencing of IB6 decreased tumor cell proliferation.17
Is there an association between IB6 expression and survival?
A meta-analysis evaluated nearly 6000 patients with lung, head and neck, breast, cervical, colorectal, gallbladder, or gastric cancer.18
Meta-analysis of overall survival in patients with high IB6 expression vs patients with low IB6 expression18
SWIPE FOR MORE >
< SWIPE FOR MORE
The lack of individual patient data resulted in reliance on summary data analyzed using meta‑regression.18
Presence of IB6 was evaluated using IHC in all studies; however, cutoff definitions for "IB6 positive" varied by study.18
In many studies, the primary aim was not to explore prognostic influence of IB6.18
CI = confidence interval; IHC = immunohistochemistry.
Could IB6 help us turn the tables in certain cancers?
IB6 is a promising therapeutic target1‑10,13,19
HIGHLY RELEVANT
A broad range of tumors are IB6 expressing, making IB6 a potential therapeutic target in many types of cancer.2‑10
HIGHLY EXPRESSED
IB6 is nearly undetectable in most adult epithelial tissue but is highly expressed in many tumor types.13
HIGHLY ACCESSIBLE
IB6 is localized to the cell surface, making it a highly accessible target for potential therapeutics.1,19
Pfizer is committed to uncovering the therapeutic possibilities of IB6 through a deeper understanding of its role in cancer
Up-regulated integrin αvβ6 [IB6] expression in various tumors and its effect on tumor progression make it a potential target for tumor imaging and therapy.
Niu et al. Cancer Lett. 2017.17
It’s time to expose another of cancer’s tricks and reveal IB6 as an important therapeutic target.
References: 1. Bandyopadhyay A, Raghavan S. Defining the role of integrin αvβ6 in cancer. Curr Drug Targets. 2009;10(7):645-652. doi:10.2174/138945009788680374 2. Elayadi AN, Samli KN, Prudkin L, et al. A peptide selected by biopanning identifies the integrin αvβ6 as a prognostic biomarker for nonsmall cell lung cancer. Cancer Res. 2007;67(12):5889-5895. doi:10.1158/0008-5472.CAN-07-0245 3. Liu H, Wu Y, Wang F, Liu Z. Molecular imaging of integrin αvβ6 expression in living subjects. Am J Nucl Med Mol Imaging. 2014;4(4):333-345. 4. Koopman Van Aarsen LA, Leone DR, Ho S, et al. Antibody-mediated blockade of integrin αvβ6 inhibits tumor progression in vivo by a transforming growth factor-β–regulated mechanism. Cancer Res. 2008;68(2):561-570. doi:10.1158/0008-5472.CAN-07-2307 5. Lawaetz M, Christensen A, Juhl K, et al. Potential of uPAR, αvβ6 integrin, and tissue factor as targets for molecular imaging of oral squamous cell carcinoma: evaluation of nine targets in primary tumors and metastases by immunohistochemistry. Int J Mol Sci. 2023;24(4):3853. doi:10.3390/ijms24043853 6. Reader CS, Vallath S, Steele CW, et al. The integrin αvβ6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. J Pathol. 2019;249(3):332-342. doi:10.1002/path.5320 7. Katoh D, Nagaharu K, Shimojo N, et al. Binding of αvβ1 and αvβ6 integrins to tenascin-C induces epithelial-mesenchymal transition-like change of breast cancer cells. Oncogenesis. 2013;2(8):e65. doi:10.1038/oncsis.2013.27 8. Bates RC, Bellovin DI, Brown C, et al. Transcriptional activation of integrin β6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma. J Clin Invest. 2005;115(2):339-347. doi:10.1172/JCI23183 9. Yang G-Y, Xu K-S, Pan Z-Q, et al. Integrin alphavbeta6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver. Cancer Sci. 2008;99(5):879-887. doi:10.1111/j.1349-7006.2008.00762.x 10. Yang G-Y, Guo S, Dong C-Y, et al. Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression. World J Gastroenterol. 2015;21(24):7457-7467. doi: 10.3748/wjg.v21.i24.7457 11. Pang X, He X, Qiu Z, et al. Targeting integrin pathways: mechanisms and advances in therapy. Signal Transduct Target Ther. 2023;8(1):1-42. doi:10.1038/s41392-022-01259-6 12. Nemeth JA, Nakada MT, Trikha M, et al. Alpha-v integrins as therapeutic targets in oncology. Cancer Invest. 2007;25(7):632-646. doi:10.1080/07357900701522638 13. Brzozowska E, Deshmukh S. Integrin alpha v beta 6 (αvβ6) and its implications in cancer treatment. Int J Mol Sci. 2022;23(20):12346. doi:10.3390/ijms232012346 14. Clere N, Renault S, Corre I. Endothelial-to-mesenchymal transition in cancer. Front Cell Dev Biol. 2020;8:747. doi:10.3389/fcell.2020.00747 15. Nystrom ML, McCulloch D, Weinreb PH, et al. Cyclooxygenase-2 inhibition suppresses αvβ6 integrin-dependent oral squamous carcinoma invasion. Cancer Res. 2006;66(22):10833-10842. doi:10.1158/0008-5472.CAN-06-1640 16. Hecht JL, Dolinski BM, Gardner HA, Violette SM, Weinreb PH. Overexpression of the αvβ6 integrin in endometrial cancer. Appl Immunohistochem Mol Morphol. 2008;16(6):543-547. doi:10.1097/PAI.0b013e31816bc5ee 17. Niu J, Li Z. The roles of integrin αvβ6 in cancer. Cancer Lett. 2017;403:128-137. doi:10.1016/j.canlet.2017.06.012 18. Desnoyers A, González C, Pérez-Segura P, Pandiella A, Amir E, Ocaña A. Integrin ανβ6 protein expression and prognosis in solid tumors: a meta-analysis. Mol Diagn Ther. 2020;24(2):143-151. Springer Nature. doi:10.1007/s40291-020-00450-1 19. Vasir JK, Labhasetwar V. Targeted drug delivery in cancer therapy. Technol Cancer Res Treat. 2005;4(4):363-374. doi:10.1177/153303460500400405
Back to Top