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calculated. For each cancer type, we calculated the average correlation co-efficient of any combination of
2-15 mRNAs.

Results: The number of co-expressed checkpoint genes with an average Spearman rho co-efficient of above
0.5 was significantly different between tumor types, ranging from 10 to 0. Thyroid carcinoma, testicular
cancer and melanoma were the three tumors with the highest number of co-expressed checkpoint mRNAs,
whereas in acute leukemia there were no co-expressed checkpoint mRNAs, as predicted. Similarly, the
nature and mix of co-stimulatory and co-inhibitory checkpoint mRNAs was different between different
tumor types, with each tumor exhibiting a different “network” of checkpoint co-expression with differing
strengths of correlations.

Conclusion: Our bioinformatic analysis indicates that both co-inhibitory and co-stimulatory checkpoint
mRNAs are co-expressed in solid malignancies in varying extents in different cancers. We propose that the
differences in these “checkpoint networks” formed on the cancer side of the IS take part in determining
cancer immunogemicity. It is tempting to speculate that these networks may also take part in determining
the potential of a tumor type to respond to the currently-available immune checkpoint inhibitors.

Biography
Raya Leibowitz completed her PhD and her MD at the Tel-Aviv university, Israel. She is currently a senior
medical oncologist (clinician-investigator) at the Sheba medical center and an assistant professor at the
department of oncology, faculty of medicine, Tel-Aviv university. Her major scientific work until now (first
and last authorship) was published in Nature Medicine, Cancer Research, Annals of oncology and Molecular
Cancer. Among other grants, she was a recipient of the “melanoma research alliance young investigator
award”, the “Gerald Kirsh” humanitarian award and the “Conquer Cancer foundation” merit award twice.

19. Sunitinib in thyroid cancer: a review of the literature

1
1
1
1
1
Giusy Elia , Silvia Martina Ferrari , Ilaria Ruffilli , Francesca Ragusa , Sabrina Rosaria Paparo , Claudia
2
1
Caruso , Poupak Fallahi , Alessandro Antonelli 1
1 Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.
2 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa,
Pisa 56126, Italy.
Sunitinib is a multi-targeted tyrosine kinase inhibitor (TKI), acting on different receptors for platelet-
derived growth factor receptors and vascular endothelial growth factor receptors, c-KIT, fms-related
tyrosine kinase 3 and RET, leading to tumor vascularization reduction, tumor cell apoptosis, and causing
tumor shrinkage.

It has been approved for the treatment of pancreatic neuroendocrine tumors, imatinib-resistant
gastrointestinal stromal tumor and renal carcinoma.

In vitro studies have been conducted on the RET/PTC1 cell, showing that sunitinib is able to target the
cytosolic MEK/ERK and SAPK/JNK pathways inhibiting cell proliferation and causing stimulation of
sodium/iodide symporter gene expression.

Also in vitro and in vivo studies conducted on anaplastic thyroid cancer cells have shown the efficacy of
sunitinib, also as first- and second-line TKI therapy in patients with advanced dedifferentiated thyroid
cancer, or medullary thyroid cancer.