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EGF AND ITS RECEPTOR AND TGFα CONCLUSION

EGFR/AKT/mTOR pathway activation could be shown The predictive and prognostic characteristics of NETs
in all entities of NETs and was observed especially in are still under investigation to individuate a pattern
tumors with high grading and poor prognosis. Typical of peculiar molecular genetic alterations in each
and atypical bronchopulmonary carcinoids [129] and kind of neoplasm. The aim is to find a correlation of
gastrointestinal-neuroendocrine tumours (GI-NETs) and specific abnormalities implicated in carcinogenesis and
P-NETs present and over-regulate EGFRs. [130] [Figure dissemination that may provide potential targets for
1] Papouchado et al. [131] in particular, described a higher tailored biotherapy.
presence of EGFR (> 91%) in GI-NETs, especially rectal
NETs, than in P-NETs (< 25%). In GEP and lung NETs, carcinogenesis and dissemination
often involves SSTRs, mTOR/Akt/PI3K and PTEN,
An elevated presence of EGFR and transforming IGF-1, VEGF, EGF, TGF, FGF and c-kit/PDGF and its
growth factor alpha (TGFα) in P-NETs was observed corresponding receptors, markers whose established
by Srivastava et al. [132] An elevated amount of secreted value may more thoroughly define an appropriate course
TGFα was detected in cultures of carcinoid tumors and of treatment.
pheochromocytomas, and the administration octreotide
and anti-EGFR monoclonal antibodies seemed to Financial support and sponsorship
reduce the secretion and the proliferative effect of Nil.
TGFα. [133] Krishnamurthy et al. [134] showed a high Conflicts of interest
expression of TGFα in GI NETs (72%) without any There are no conflicts of interest.
correlation with tumor size, grading, and other pathologic
features, but only depending on the technique used Patient consent
(immunohistochemistry or northern blot analysis). [133] In No patient involved.
rectal NENs TGF-α expression seemed to be increased
in lesions larger than 5 mm and tumors with higher Ki67 Ethics approval
index. [135] Despite the heterogeneity of these results, This article does not contain any studies with human
EGFR and its signal transduction pathways (RAS-RAF- participants or animals.
MAPK) might represent an interesting target for the
treatment of NETs. REFERENCES

In fact, a synergistic effect in determining apoptosis in 1. Cives M, Strosberg J. An update on gastroenteropancreatic
atypical carcinoid cell lines was demonstrated by the neuroendocrine tumours. Oncology (Williston Park)
association of epidermal growth factor (EGF) receptor 2014;28:749-56, 758.
inhibitors (erlotinib) with everolimus in in-vitro 2. Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Kloppel
studies. [129] G, Komminoth P, Solcia E. Nomenclature and classification
of neuroendocrine neoplasms of the digestive system. In WHO
Classification of Tumours of the Digestive System, Eds. FT
A phase II trial evaluated gefitinib in 96 pretreated Bosman, F Carneiro, RH Hruban & N Theise. Lyon: IARC Press.
patients affected by GEP-NETs achieved prolonged 2010. p. 13-14.
disease control with rare objective responses; the study 3. Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC.
drug was well-tolerated. [136] Gastroenteropancreatic high-grade neuroendocrine carcinoma.
Cancer 2014;120:2814-23.
4. La Rosa S, Sessa F. High-grade poorly differentiated neuroendocrine
OTHER TYROSINE KINASE INHIBITORS carcinomas of the gastroenteropancreatic system: from morphology
AND IMMUNOTHERAPY to proliferation and back. Endocr Pathol 2014;25:193-8.
5. Capdevila J, Salazar R, Halperin I, Abad A, Yao JC. Innovations
Beta fibroblast growth factor (bFGF) and c-kit/Platelet therapy: mammalian target of rapamycin (mTOR) inhibitors for
the treatment of neuroendocrine tumours. Cancer Metastasis Rev
Derived Growth Factor (PDGF) inhibitors are being 2011;30:27-34.
developed, based upon the variable expression of bFGF, 6. Capdevila J, Tabernero J. A shining light in the darkness for the
c-kit and PDGF in NETs. [137-139] treatment of pancreatic neuroendocrine tumours. Cancer Discov
2011;1:213-21.
Despite little systematic and rigorous in-depth analysis 7. Hilfenhaus G, Gohrig A, Pape UF, Neumann T, Jann H, Zdunek D,
Hess G, Stassen JM, Wiedenmann B, Detjen K, Pavel M, Fischer
of immunotherapy in NETs (interferon and dendritic C. Placental growth factor supports neuroendocrine tumour growth
cell vaccines), the recent progress in targeting of and predicts disease prognosis in patients. Endocr Relat Cancer
Cytotoxic T lymphocyte antigen-4 and PD-1 provide 2013;20:305-19.
opportunities for future advances. [140] Further studies 8. Vallières E, Shepherd FA, Crowley J, Van Houtte P, Postmus
are necessary to examine the variable expression of PE, Carney D, Chansky K, Shaikh Z, Goldstraw P; International
Association for the Study of Lung Cancer International Staging
PD-1, PD-L1/L2 in NENs. Committee and Participating Institutions. The IASLC Lung Cancer
336
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 31, 2016 ¦