Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Research

p90RSK pathway inhibition synergizes with cisplatin in TMEM16A overexpressing head and neck cancer

Authors: Abdulkader Yassin-Kassab, Suman Chatterjee, Nayel Khan, Nathaniel Wang, Vlad C. Sandulache, Eric H-B. Huang, Timothy F. Burns, Umamaheswar Duvvuri

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Head and neck squamous cell carcinoma (HNSCC) constitutes one of the most common types of human cancers and often metastasizes to lymph nodes. Platinum-based chemotherapeutic drugs are commonly used for treatment of a wide range of cancers, including HNSCC. Its mode of action relies on its ability to impede DNA repair mechanisms, inducing apoptosis in cancer cells. However, due to acquired resistance and toxic side-effects, researchers have been focusing on developing novel combinational therapeutic strategies to overcome cisplatin resistance. In the current study, we identified p90RSK, an ERK1/2 downstream target, as a key mediator and a targetable signaling node against cisplatin resistance. Our results strongly support the role of p90RSK in cisplatin resistance and identify the combination of p90RSK inhibitor, BI-D1870, with cisplatin as a novel therapeutic strategy to overcome cisplatin resistance. In addition, we have identified TMEM16A expression as a potential upstream regulator of p90RSK through the ERK pathway and a biomarker of response to p90RSK targeted therapy in the context of cisplatin resistance.
Appendix
Available only for authorised users
Literature
1.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Stat 2022 CA: cancer J Clin. 2022;72:7–33.
2.
3.
Chen X, Wu Y, Dong H, Zhang CY, Zhang Y. Platinum-based agents for individualized cancer treatment. Curr Mol Med. 2013;13:1603–12.PubMedCrossRef
4.
Dilruba S, Kalayda GV. Platinum-based drugs: past, present and future. Cancer Chemother Pharmacol. 2016;77:1103–24.PubMedCrossRef
5.
Baharuddin P, et al. Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines. Oncol Rep. 2016;35:13–25.PubMedCrossRef
6.
7.
Tao K, et al. Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells. Biomedical Rep. 2016;4:365–8.CrossRef
8.
Zhang P, Gao WY, Turner S, Ducatman BS. Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro. Mol Cancer. 2003;2:1.PubMedPubMedCentralCrossRef
9.
Achkar IW, et al. Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway. J Translational Med. 2018;16:96.CrossRef
10.
Carriere A, Ray H, Blenis J, Roux PP. The RSK factors of activating the Ras/MAPK signaling cascade. Front Bioscience: J Virtual Libr. 2008;13:4258–75.CrossRef
11.
12.
Pambid MR, et al. Overcoming resistance to Sonic hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma. Pediatr Blood Cancer. 2014;61:107–15.PubMedCrossRef
13.
Godse NR, et al. TMEM16A/ANO1 inhibits apoptosis Via downregulation of Bim expression. Clin cancer Research: Official J Am Association Cancer Res. 2017;23:7324–32.CrossRef
14.
Wang H, et al. A mutual activation loop between the ca(2+)-activated chloride channel TMEM16A and EGFR/STAT3 signaling promotes breast cancer tumorigenesis. Cancer Lett. 2019;455:48–59.PubMedCrossRef
15.
16.
Yu W et al. Acquisition of Cisplatin Resistance shifts Head and Neck squamous cell Carcinoma Metabolism toward neutralization of oxidative stress. Cancers 12 (2020).
17.
Ashton JC. Drug combination studies and their synergy quantification using the Chou-Talalay method–letter. Cancer Res. 2015;75:2400.PubMedCrossRef
18.
Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70:440–6.PubMedCrossRef
19.
Henderson YC, et al. A high-throughput Approach to identify effective systemic agents for the treatment of anaplastic thyroid carcinoma. J Clin Endocrinol Metab. 2021;106:2962–78.PubMedPubMedCentralCrossRef
20.
Burns TF, et al. Inhibition of TWIST1 leads to activation of oncogene-induced senescence in oncogene-driven non-small cell lung cancer. Mol cancer Research: MCR. 2013;11:329–38.PubMedCrossRef
21.
Moffat J, et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell. 2006;124:1283–98.PubMedCrossRef
22.
Chatterjee S, Huang EH, Christie I, Kurland BF, Burns TF. Acquired Resistance to the Hsp90 inhibitor, Ganetespib, in KRAS-Mutant NSCLC is mediated via reactivation of the ERK-p90RSK-mTOR Signaling Network. Mol Cancer Ther. 2017;16:793–804.PubMedPubMedCentralCrossRef
23.
Bill A, et al. Small molecule-facilitated degradation of ANO1 protein: a new targeting approach for anticancer therapeutics. J Biol Chem. 2014;289:11029–41.PubMedPubMedCentralCrossRef
24.
Britschgi A, et al. Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling. Proc Natl Acad Sci USA. 2013;110:E1026–1034.PubMedPubMedCentralCrossRef
25.
26.
Carriere A, et al. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biology: CB. 2008;18:1269–77.PubMedCrossRef
27.
Kang S, et al. p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. J Clin Investig. 2010;120:1165–77.PubMedPubMedCentralCrossRef
28.
Sapkota GP, et al. BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007;401:29–38.PubMedCrossRef
29.
Shiwarski DJ, et al. To grow or go: TMEM16A expression as a switch between tumor growth and metastasis in SCCHN. Clin cancer Research: Official J Am Association Cancer Res. 2014;20:4673–88.CrossRef
30.
Ruiz C, et al. Enhanced expression of ANO1 in head and neck squamous cell carcinoma causes cell migration and correlates with poor prognosis. PLoS ONE. 2012;7:e43265.ADSPubMedPubMedCentralCrossRef
31.
Okuyama K, Yanamoto S. TMEM16A as a potential treatment target for head and neck cancer. J Experimental Clin Cancer Res. 2022;41:196.CrossRef
32.
Haddad RI, et al. Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2018;29:1130–40.PubMedCrossRef
33.
34.
Park YY, Nam HJ, Do M, Lee JH. The p90 ribosomal S6 kinase 2 specifically affects mitotic progression by regulating the basal level, distribution and stability of mitotic spindles. Exp Mol Med. 2016;48:e250.PubMedPubMedCentralCrossRef
35.
Houles T, Roux PP. Defining the role of the RSK isoforms in cancer. Sem Cancer Biol. 2018;48:53–61.CrossRef
36.
Youn M, Gomez JO, Mark K, Sakamoto KM. RSK isoforms in Acute myeloid leukemia. Biomedicines 9 (2021).
37.
Chiu CF, et al. Antitumor effects of BI-D1870 on human oral squamous cell carcinoma. Cancer Chemother Pharmacol. 2014;73:237–47.PubMedCrossRef
38.
van Jaarsveld, et al. The kinase RSK2 modulates the sensitivity of ovarian cancer cells to cisplatin. Eur J cancer (Oxford England: 1990). 2013;49:345–51.CrossRef
39.
Abdulrahman N, et al. Inhibition of p90 ribosomal S6 kinase potentiates cisplatin activity in A549 human lung adenocarcinoma cells. J Pharm Pharmacol. 2020;72:1536–45.PubMedCrossRef
40.
Kleih M, et al. Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 2019;10:851.PubMedPubMedCentralCrossRef
41.
Chaney SG, Campbell SL, Bassett E, Wu Y. Recognition and processing of cisplatin- and oxaliplatin-DNA adducts. Crit Rev Oncol/Hematol. 2005;53:3–11.PubMedCrossRef
42.
Martens-de SR, Kemp, et al. DNA-bound platinum is the major determinant of cisplatin sensitivity in head and neck squamous carcinoma cells. PLoS ONE. 2013;8:e61555.ADSCrossRef
43.
44.
Abdullah N et al. Malformin-A1 (MA1) sensitizes Chemoresistant Ovarian Cancer cells to Cisplatin-Induced apoptosis. Molecules 26 (2021).
Metadata
Title
p90RSK pathway inhibition synergizes with cisplatin in TMEM16A overexpressing head and neck cancer
Authors
Abdulkader Yassin-Kassab
Suman Chatterjee
Nayel Khan
Nathaniel Wang
Vlad C. Sandulache
Eric H-B. Huang
Timothy F. Burns
Umamaheswar Duvvuri
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11892-9

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue

Research

Drug-resistant profiles of extracellular vesicles predict therapeutic response in TNBC patients receiving neoadjuvant chemotherapy

Research

EMP3 as a prognostic biomarker correlates with EMT in GBM

Research

Efficacy and safety analysis of hypofractionated and conventional fractionated radiotherapy in postoperative breast cancer patients

Research

IDH1 mutation is detectable in plasma cell-free DNA and is associated with survival outcome in glioma patients

Research

Causal inference between pernicious anemia and cancers: a bidirectional two-sample mendelian randomization analysis

Research

Analysis of related factors for pathological upgrading of cervical biopsy from CIN3 to cancer after conical resection
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits