Page 32 - Read Online
P. 32
cells. Through competitive binding to EGFR References
ligands, panitumumab prevents EGFR dimerization, 1. Sarmiento R, Longo R, Gasparini G. Antiangiogenic therapy
auto-phosphorylation and signaling, thereby inhibiting of colorectal cancer: state of the art, challenges and new
proliferation and promoting apoptosis. [78] A Phase III approaches. Int J Biol Markers 2012;27:e286-94.
study, the PRIME trial, evaluated the combination of 2. Gavalas NG, Liontos M, Trachana SP, Bagratuni T, Arapinis C,
FOLFOX4 with panitumumab or FOLFOX4 alone as Liacos C, Dimopoulos MA, Bamias A. Angiogenesis-related
fi rst-line treatment. [79] As compared to chemotherapy pathways in the pathogenesis of ovarian cancer. Int J Mol Sci
alone, the combination therapy signifi cantly 2013;14:15885-909.
improved PFS and increased RR in patients with 3. Pang RW, Poon RT. Clinical implications of angiogenesis in
wild-type KRAS. A non-signifi cant increase in OS 4. cancers. Vasc Health Risk Manag 2006;2:97-108.
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS,
was also observed. In order to assess the effi cacy and Dvorak HF. Tumor cells secrete a vascular permeability
safety of FOLFOX4 with panitumumab as compared factor that promotes accumulation of ascites fl uid. Science
to FOLFOX4 alone according to KRAS (exon 2-4) 1983;219:983-5.
and NRAS (exon 2-4) mutation status, data from the 5. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M,
PRIME trial were analyzed. [80] Patients without any Ras Wu XF, Breitman ML, Schuh AC. Failure of blood-island
mutation who were treated with panitumumab had a formation and vasculogenesis in Flk-1-defi cient mice. Nature
signifi cantly longer OS and PFS than those treated with 6. 1995;376:62-6.
Kawasaki T, Kitsukawa T, Bekku Y, Matsuda Y, Sanbo M,
chemotherapy alone. Yagi T, Fujisawa H. A requirement for neuropilin-1 in
Regorafenib embryonic vessel formation. Development 1999;126:4895-902.
7. Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of
Regorafenib is an inhibitor of PDGFRs, c-KIT, FGF the Flt-1 receptor tyrosine kinase in regulating the assembly of
[81]
receptor and VEGF1-3. In the pivotal Phase III vascular endothelium. Nature 1995;376:66-70.
study, the CORRECT trial, patients with mCRC 8. Robinson CJ, Stringer SE. The splice variants of vascular
who had progressed after undergoing treatment with endothelial growth factor (VEGF) and their receptors.
approved drugs were randomly assigned to regorafenib J Cell Sci 2001;114:853-65.
or placebo. As compared to placebo, treatment 9. Kleespies A, Guba M, Jauch KW, Bruns CJ. Vascular
[82]
endothelial growth factor in esophageal cancer. J Surg Oncol
with regorafenib signifi cantly prolonged OS and PFS, 2004;87:95-104.
suggesting a potential new line of therapy with survival 10. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA,
benefi ts for patients who have progressed after all Dixit V, Ferrara N. Vascular endothelial growth factor regulates
standard therapies. endothelial cell survival through the phosphatidylinositol
3’-kinase/Akt signal transduction pathway. Requirement for
Afl ibercept Flk-1/KDR activation. J Biol Chem 1998;273:30336-43.
Afl ibercept is a recently developed, multiple 11. Robinson KW, Sandler AB. EGFR tyrosine kinase inhibitors:
angiogenic factors trap that inhibits not only VEGF-A, difference in effi cacy and resistance. Curr Oncol Rep
2013;15:396-404.
VEGF-B and PLGF, from activating their native 12. Mitsudomi T. Molecular epidemiology of lung cancer and
receptor (VEGFR-1). [83,84] Afl ibercept has a higher geographic variations with special reference to EGFR
VEGF-A binding affi nity than bevacizumab. The mutations. Transl Lung Cancer Res 2014;3:205-11.
velour trial evaluated FOLFIRI plus afl ibe receptor 13. Li Q, Wang D, Li J, Chen P. Clinicopathological and
FOLFIRI alone after progression on an oxaliplain-based prognostic signifi cance of HER-2/neu and VEGF expression in
[85]
chemotherapy. As compared to chemotherapy alone, the colon carcinomas. BMC Cancer 2011;11:277.
addition of bevacizumab signifi cantly improved OS. 14. Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM.
Expression of the HER1-4 family of receptor tyrosine kinases
Conclusion in breast cancer. J Pathol 2003;200:290-7.
15. Reichelt U, Duesedau P, Tsourlakis M, Quaas A, Link BC,
The clinical application of molecular targeted drugs has Schurr PG, Kaifi JT, Gros SJ, Yekebas EF, Marx A, Simon R,
improved the survival of patients with GI cancers. We Izbicki JR, Sauter G. Frequent homogeneous HER-2
believe that both the identifi cation of novel targets and amplifi cation in primary and metastatic adenocarcinoma of the
esophagus. Mod Pathol 2007;20:120-9.
the development of new drugs targeting several important 16. Gravalos C, Jimeno A. HER2 in gastric cancer: a new
pathways such as c-MET, rearranged during transfection, prognostic factor and a novel therapeutic target. Ann Oncol
MEK and IGF/IGFR will contribute to further 2008;19:1523-9.
improvements in treatment results and the realization of 17. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S,
personalized treatments for GI cancer. Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K,
Isola J. Amplifi cation of HER-2 in gastric carcinoma:
Financial support and sponsorship association with topoisomerase II alpha gene amplifi cation,
intestinal type, poor prognosis and sensitivity to trastuzumab.
Nil. Ann Oncol 2005;16:273-8.
Confl icts of interest 18. Begnami MD, Fukuda E, Fregnani JH, Nonogaki S,
Montagnini AL, da Costa WL Jr, Soares FA. Prognostic
There are no confl icts of interest. implications of altered human epidermal growth factor
168 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦