SSTR2 and epi-NET

The Research Group focuses on research associated with the SSTR2 and epiNET in Head & Neck Cancer.

Professor Matt Lechner

Mr Matt Lechner, PhD, MD, FRCS (ORL-HNS), FHEA

Associate Professor of Surgery

UCL Cancer Institute

SSTR2 and epi-NET Programme

This is one of the flagship projects of the newly established UCL/UCLH Cancer Biomarker Centre. The planned work is based on our discoveries in Nasopharyngeal cancer and Olfactory Neuroblastoma

Project Leads

  • Jacklyn Liu (3rd year PhD student): Sinonasal cancers, nasopharyngeal cancer, SCLC, NETs, neuroendocrine prostate cancers, virally induced NETs 
  • Yvonne Power: Pituitary adenoma and brain cancers.

SSTR2 Cancer Programme and epi-NET (companion diagnostic, prognostic biomarker, imaging and therapy)

We recently completed studies assessing the role of the somatostatin receptor 2 (SSTR2) in sinonasal cancers, with a particular focus on nasopharyngeal cancer (n=404 patients) and olfactory neuroblastoma (n=402 patients). With the promising efficacy of SSTR2 as a biomarker and therapeutic target in neuroendocrine tumours, we aim to apply the following to all SSTR2-positive cancers, incl. SCLC, GI tract neuroendocrine tumours, olfactory neuroblastoma, pituitary adenoma, brain cancers, nasopharyngeal cancer and some forms of prostate cancer.

Milestone 1: Optimisation of companion diagnostic biomarker

  • Optimization and automatization of protocol for use as companion diagnostic and prognostic biomarker and automated image analysis (AI scoring algorithm of stained images) – framework for further pipeline development.
  • Cancer landscape analysis of SSTR2 with a focus on head and neck cancers and brain tumours and correlation with clinical outcomes (Brain UK ethical approval obtained).

Milestone 2: Identification of the mechanism of SSTR2 overexpression and targetable vulnerabilities

  • Multi-dimensional data analysis 
  • Functional validations in vitro

Milestone 3: In vitro and in vivo testing of SSTR2-targeting agents and targeting related pathways in preparation for Clinical Phase I trials of most promising compounds (with industry partner)

We are currently investigating the molecular basis of SSTR2 overexpression in these tumours as part of the epi-NET programme.

Collaborators: International networks, incl. EUSICA, INSICA-Brain and industry partners

1. Clinical Outcomes, Kadish-INSICA Staging and Therapeutic Targeting of SSTR2 in Olfactory Neuroblastoma. M. Lechner, et al.; European Journal of Cancer. 2022; 162:221-236; doi: 10.1016/j.ejca.2021.09.046.

2. SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target. O. Emanuel, J. Liu, V.H. Schartinger, W.L. Nei, Y.Y. Chan, C.M. Tsang, 
H. Riechelmann, L. Masterson, J. Haybaeck, U. Oppermann, S.M. Willems, M.L. Ooft, G. Wollmann, D. Howard, B. Vanhaesebroeck, V.J. Lund, G. Royle, M.L.K. Chua, K.W. Lo, P. Busson, and M. Lechner; Cancers. 2021; 13(19), 4944; https://doi.org/10.3390/cancers13194944

3. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. M. Lechner, et al.; Nature Communications. 2021; 12(1):117. doi: 10.1038/s41467-020-20308-8.

4. PSMA PET Imaging and Therapy in Adenoid Cystic Carcinoma and Other Salivary Gland Cancers: A Systematic Review. B.F. Tan, W.C.C. Tan, F.Q. Wang, M. Lechner, V.H.  Schartinger, D.S.W. Tan, K.S.H. Loke, W.L. Nei; Cancers (Basel). 2022; 14(15):3585. doi: 10.3390/cancers14153585. 

5. A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution. T. Zhu, J. Liu, S. Beck, S. Pan, D. Capper, M. Lechner, C. Thirlwell, C.E. Breeze, A.E. Teschendorff. Nature Methods. 2022;19(3):296-306; doi: 10.1038/s41592-022-01412-7.

6. The genomics and epigenetics of olfactory neuroblastoma: A systematic review. R.P. Kaur, E. Izumchenko, D.M. Blakaj, N. Mladkova, M. Lechner, T.L. Beaumont; Laryngoscope Investigative Otolaryngology. 2021; doi.org/10.1002/lio2.597

7. Ultra-fast scalable estimation of single-cell differentiation potency from scRNA-Seq data; A. Teschendorff, A.K. Maity, X. Hu, C. Weiyan, M. Lechner; Bioinformatics. 2021, 12; 37(11): 1528-1534. doi: 10.1093/bioinformatics/btaa987. 

8. Signatures of copy number alterations in human cancer. C.D. Steele, A. Abbasi, S.M.A. Islam, A.L. Bowes, A. Khandekar, K. Haase, S. Hames-Fathi, D. Ajayi, A. Verfaillie, P. Dhami, A. McLatchie, M. Lechner, N. Light, A. Shlien, D. Malkin, A. Feber, P. Proszek, T. Lesluyes, F. Mertens, A.M. Flanagan, M. Tarabichi,, P. Van Loo, L.B. Alexandrov, N. Pillay; Nature. 2022; doi: 10.1038/s41586-022-04738-6.

9. Novel Biomarkers in Sinonasal Cancers: From Bench to Bedside. M. Lechner et al.; Current Oncology Reports. 2020; 22(10):106. 

10. Precision medicine in rare tumors and the need for multicenter trials and international collaboratives: Sinonasal cancer as paradigm. P. Bossi, M. Hermsen, M. Lechner, A. Franchi. Oral Oncology. 2020;104737. doi:10.1016/j.oraloncology.2020.104737

11. Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation? L. Masterson, J. Howard, J. Gonzalez-Cruz, C. Jackson, C.  Barnett, L Overton, H. Liu, R. Ladwa, F. Simpson, M. McGrath, B. Wallwork, T.M. Jones, C. Ottensmeier, M.L.K. Chua, C. Perry, R. Khanna, B. Panizza, S. Porceddu & M. Lechner; International Journal of Cancer. 2020;146(8):2305-2314.

12. Pan-cancer deconvolution of tumour composition using DNA methylation. A. Chakravarthy, A. Furness, K. Joshi, E. Ghorani, K. Ford, M.J. Ward, E.V. King, M. Lechner, T. Marafioti, S.A. Quezada, G.J. Thomas, A. Feber, T.R. Fenton. Nature Communications. 2018; 13;9(1): 3220.

Funders

Head and neck cancer research