Theranostics 2022; 12(3):1204-1219. doi:10.7150/thno.64347 This issue Cite

Research Paper

Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes

Maria R. Jubran1, Daniela Vilenski1, Efrat Flashner-Abramson1, Efraim Shnaider1, Swetha Vasudevan1, Ariel M. Rubinstein1, Amichay Meirovitz2, Shay Sharon3, David Polak4✉, Nataly Kravchenko-Balasha1✉

1. The Institute of Biomedical and Oral Research, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
2. Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
3. Department of Oral and Maxillofacial Surgery, The Hebrew University and Hadassah Medical Center, Jerusalem, Israel.
4. Department of Periodontics, Faculty of Dental Medicine, The Hebrew University and Hadassah Medical Center, Jerusalem, Israel.

Citation:
Jubran MR, Vilenski D, Flashner-Abramson E, Shnaider E, Vasudevan S, Rubinstein AM, Meirovitz A, Sharon S, Polak D, Kravchenko-Balasha N. Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes. Theranostics 2022; 12(3):1204-1219. doi:10.7150/thno.64347. https://www.thno.org/v12p1204.htm
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Abstract

Graphic abstract

Therapeutic strategies for advanced head and neck squamous carcinoma (HNSCC) consist of multimodal treatment, including Epidermal Growth Factor Receptor (EGFR) inhibition, immune-checkpoint inhibition, and radio (chemo) therapy. Although over 90% of HNSCC tumors overexpress EGFR, attempts to replace cytotoxic treatments with anti-EGFR agents have failed due to alternative signaling pathways and inter-tumor heterogeneity.

Methods: Using protein expression data obtained from hundreds of HNSCC tissues and cell lines we compute individualized signaling signatures using an information-theoretic approach. The approach maps each HNSCC malignancy according to the protein-protein network reorganization in every tumor. We show that each patient-specific signaling signature (PaSSS) includes several distinct altered signaling subnetworks. Based on the resolved PaSSSs we design personalized drug combinations.

Results: We show that simultaneous targeting of central hub proteins from each altered subnetwork is essential to selectively enhance the response of HNSCC tumors to anti-EGFR therapy and inhibit tumor growth. Furthermore, we demonstrate that the PaSSS-based drug combinations lead to induced expression of T cell markers and IFN-γ secretion, pointing to higher efficiency of the immune response.

Conclusion: The PaSSS-based approach advances our understanding of how individualized therapies should be tailored to HNSCC tumors.

Keywords: precision medicine, targeted therapy, head and neck squamous cell carcinoma, information-theoretic approach, patient-specific signaling signatures


Citation styles

APA
Jubran, M.R., Vilenski, D., Flashner-Abramson, E., Shnaider, E., Vasudevan, S., Rubinstein, A.M., Meirovitz, A., Sharon, S., Polak, D., Kravchenko-Balasha, N. (2022). Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes. Theranostics, 12(3), 1204-1219. https://doi.org/10.7150/thno.64347.

ACS
Jubran, M.R.; Vilenski, D.; Flashner-Abramson, E.; Shnaider, E.; Vasudevan, S.; Rubinstein, A.M.; Meirovitz, A.; Sharon, S.; Polak, D.; Kravchenko-Balasha, N. Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes. Theranostics 2022, 12 (3), 1204-1219. DOI: 10.7150/thno.64347.

NLM
Jubran MR, Vilenski D, Flashner-Abramson E, Shnaider E, Vasudevan S, Rubinstein AM, Meirovitz A, Sharon S, Polak D, Kravchenko-Balasha N. Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes. Theranostics 2022; 12(3):1204-1219. doi:10.7150/thno.64347. https://www.thno.org/v12p1204.htm

CSE
Jubran MR, Vilenski D, Flashner-Abramson E, Shnaider E, Vasudevan S, Rubinstein AM, Meirovitz A, Sharon S, Polak D, Kravchenko-Balasha N. 2022. Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes. Theranostics. 12(3):1204-1219.

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