Revisiones en Cáncer 00077 / http://dx.doi.org/10.20960/revcancer.00077
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Revisión

Nuevos fármacos más allá de la inmunoterapia en cáncer escamoso de cabeza y cuello


Alberto Jacobo Cunquero Tomás, Alfonso Berrocal Jaime

Prepublicado: 2024-06-10
Publicado: 2024-08-01

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El cáncer de cabeza y cuello (HNSCC) representa un desafío clínico significativo, especialmente en sus formas recurrentes y metastásicas. A pesar de los avances con agentes inmunoterápicos como pembrolizumab y nivolumab, más del 50 % de los pacientes no responden eficazmente. Este artículo revisa las terapias emergentes centradas en dianas moleculares específicas y no exclusivamente inmunológicas. Se destacan desarrollos en anticuerpos inmunoconjugados (ADC) como el sacituzumab govitecán y el enfortumab vedotina, que muestran resultados prometedores en estudios de fase II. También se examinan las vías de señalización como PI3K/AKT/mTOR y MAPK, que son cruciales en la tumorigénesis y en la resistencia a tratamientos. Además, se abordan terapias dirigidas, como los inhibidores de ciclinas, y terapias combinadas que podrían ofrecer nuevas esperanzas para abordar la resistencia a los tratamientos actuales. Este compendio resalta la necesidad de continuar explorando y desarrollando terapias que aborden las complejidades y la heterogeneidad del HNSCC para mejorar los resultados clínicos.

Palabras Clave: HNSCC. Anticuerpos inmunoconjugados. Anticuerpos biespecíficos. Terapias dirigidas. Radiosensibilizador.



Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomized, open-label, phase 3 study. Lancet. 2019;394(10212):1915-28.
DOI: 10.1016/S0140-6736(19)32591-7
Ferris RL, Blumenschein Jr G, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.N Engl J Med 2016;375(19):1856-67.
DOI: 10.1056/NEJMoa1602252
Cohen EEW 1, Soulières D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019;393(10167):156-67.
DOI: 10.1016/S0140-6736(18)31999-8
Lee NY, Ferris RL Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol 2021;22(4):450-62.
DOI: 10.1016/S1470-2045(20)30737-3
Machiles JP, Tao Y, Licitra L, et al. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol 2024;25(5):572-87.
DOI: 10.1016/S1470-2045(24)00100-1
Pérez Sayáns M, Chamorro Petronacci CM, Lorenzo Pouso AI, et al. Comprehensive Genomic Review of TCGA Head and Neck Squamous Cell Carcinomas (HNSCC). J Clin Med 2019;8(11):1896.
DOI: 10.3390/jcm8111896
The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015;517(7536):576-82.
DOI: 10.1038/nature14129
Warren EAK, Anil J, D Castro P, et al. Human epidermal growth factor receptor 2 expression in head and neck squamous cell carcinoma: Variation within and across primary tumor sites, and implications for antigen-specific immunotherapy. Head Neck 2021;43(7):1983-94.
DOI: 10.1002/hed.26662
Lui VW, Hedberg ML, Li H, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov 2013;3:761-9.
DOI: 10.1158/2159-8290.CD-13-0103
Hu L, Hofmann J, Lu Y, et al. Inhibition of phosphatidylinositol 3´-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res 2002;62:1087-92.
Seiwert TY, Zuo Z, Keck MK, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res 2015;21:632-41.
DOI: 10.1158/1078-0432.CCR-13-3310
Li Q, Tie Y, Alu A, et al. Targeted therapy for head and neck cancer: signaling pathways and clinical studies. Signal Transduct Target Ther 2023;8(1):31.
DOI: 10.1038/s41392-022-01297-0
Ngan HL, Liu Y, Fong AY, et al. MAPK pathway mutations in head and neck cancer affect immune microenvironments and ErbB3 signaling. Life Sci Alliance 2020;3(6):e201900545.
DOI: 10.26508/lsa.201900545
Arnold L, Enders J, Thomas SM. Activated HGF-c-Met axis in head and neck cancer. Cancers 2017;9:169.
DOI: 10.3390/cancers9120169
Rothenberger NJ, Stabile LP. Hepatocyte growth factor/c-met signaling in head and neck cancer and implications for treatment. Cancers 2017;9:39.
DOI: 10.3390/cancers9040039
Raj S, Kumar Kesari K, Kumar A, et al. Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer. Mol Cancer 2022;21(1):31.
DOI: 10.1186/s12943-022-01503-1
Vassilakopoulou M, Psyrri A, Argiris A. Targeting angiogenesis in head and neck cancer. Oral Oncol 2015;51:409-15.
DOI: 10.1016/j.oraloncology.2015.01.006
Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res 2005;11:1434-40.
DOI: 10.1158/1078-0432.CCR-04-1870
Yang XH, Feng ZE, Yan M, et al. XIAP is a predictor of cisplatin­ based chemotherapy response and prognosis for patients with advanced head and neck cancer. PLoS One 2012;7:e31601.
DOI: 10.1371/journal.pone.0031601
Dougan SK, Dougan M. Regulation of innate and adaptive antitumor immunity by IAP antagonists. Immunotherapy 2018;10:787-96.
DOI: 10.2217/imt-2017-0185
Hamilton E, Infante JR. Targeting CDK4/6 in patients with cancer. Cancer Treat Rev 2016;45:129-38.
DOI: 10.1016/j.ctrv.2016.03.002
Metrangolo V, Engerlholm L. Antibody-Drug Conjugates: The Dynamic Evolution from Conventional to Next-Generation Constructs. Cancers (Basel) 2024;16(2):447.
DOI: 10.3390/cancers16020447
Fu Z, Li S, Han S, et al. Antibody drug conjugate: The “biological missile” for targeted cancer therapy. Signal Transduct Target Ther 2022;7(1):93.
DOI: 10.1038/s41392-022-00947-7
Shvartsur A, Bonavida B. Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes Cancer 2015;6(3-4):84-105.
DOI: 10.18632/genesandcancer.40
Zhang B, Gao S, Li R, et al. Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation. BMC Cancer 2020;20(1):815.
DOI: 10.1186/s12885-020-07257-7
Michel L, Jimeno A, Sukari A, et al. Sacituzumab govitecán (SG) in patients (pts) with relapsed/refractory (R/R) advanced head and neck squamous cell carcinoma (HNSCC): Results from the phase II TROPiCS-03 basket trial. ESMO Congress 2023.
DOI: 10.1016/j.annonc.2023.09.2005
Sanders C, Lau JF, Dietrich D, et al. Nectin-4 is widely expressed in head and neck squamous cell carcinoma. Oncotarget 2022;13:1166-73.
DOI: 10.18632/oncotarget.28299
Swiecicki P, Yilmaz E, Rosenberg AJ, et al. Enfortumab vedotina in the previously treated advanced head and neck cancer (HNC) cohort of EV-202. ASCO Congress 2023. J Clin Oncol 2023;41(16):6017.
DOI: 10.1200/JCO.2023.41.16_suppl.6017
Lyon R, Jonas M, Frantz C, et al. SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. Mol Cancer Ther 2023;22(12):1444-53.
DOI: 10.1158/1535-7163.MCT-22-0817
Hollebecque A, López J, Piha-paul SA, et al. SGN-B6A, An Integrin Beta-6 Targeted Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors: Updated Results From a Phase 1 Study (SGNB6A-001). ASCO Congress 2023.
DOI: 10.1136/jitc-2022-SITC2022.0731
Xue L, Han Y, Zhang Q, et al. Efficacy and Safety of a Novel Anti EGFR ADC MRG003 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck patients. ESMO Congress 2023.
DOI: 10.1016/j.annonc.2023.09.2083
Breij EC, De Goeij BE, Verploegen S, et al. An antibody-drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors. Cancer Res 2014;74(4):1214-26.
DOI: 10.1158/0008-5472.CAN-13-2440
Seidel UJ, Schlegel P, Lang P. Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies. Front Immunol 2013;4:76.
DOI: 10.3389/fimmu.2013.00076
Versteeg HH. Tissue factor: old and new links with cancer biology. Semin Thromb Hemost 2015;41:747-55.
DOI: 10.1055/s-0035-1556048
De Bono JS, Harris JR, Burn SM, et al. Systematic study of tissue factor expression in solid tumors. Cancer Rep (Hoboken) 2023;6(2):e1699.
De Bono JS, Concin N, Hong DS, et al. Tisotumab vedotina in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1–2 trial. Lancet Oncol 2019;20(3):383-93.
DOI: 10.1016/S1470-2045(18)30859-3
Cirauqui B, Salas S, William W, et al. Tisotumab vedotina (TV) in squamous cell carcinoma of head and neck (SCCHN): interim analysis from innovaTV 207. AACR Congress 2023.
DOI: 10.1158/1538-7445.AM2023-CT164
Chang HW, Frey G, Liu H, et al. Generating tumor-selective conditionally active biologic anti-CTLA4 antibodiesvia protein-associated chemical switches. Proc Natl Acad Sci USA 2021;118(9):e2020606118.
DOI: 10.1073/pnas.2020606118
Debebe Z. Rathmell WK. Ror2 as a therapeutic target in cancer. Pharmacol Ther 2015;150:143-8.
DOI: 10.1016/j.pharmthera.2015.01.010
Lu C, Wang X, Zhu H, et al. Over-expression of ROR2 and Wnt5a cooperatively correlates with unfavorable prognosis in patients with non-small cell lung cancer. Oncotarget 2015;6:24912-21.
DOI: 10.18632/oncotarget.4701
Ho AL, Adkins D, Lorch JH, et al. A phase 2 open-label study of conditionally active biologic ozuriftamab vedotina (BA3021) in failed PD-1/L1 treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. ASCO Congress 2023.
DOI: 10.1200/JCO.2023.41.16_suppl.TPS6107
Li J, Wang R, Gao J. Novel anticancer drugs approved in 2020. Drug Discov Ther 2021;15(1):44-7.
DOI: 10.5582/ddt.2021.01013
Kobayashi H, Furusawa A, Rosenberg A, et al. Near-infrared photoimmunotherapy of cancer: a new approach that kills cancer cells and enhances anti-cancer host immunity. Int Immunol 2021;33(1):7-15.
DOI: 10.1093/intimm/dxaa037
Sato K, Ando K, Okuyama S, et al. Photoinduced ligand release from a silicon phthalocyanine dye conjugated with monoclonal antibodies: a mechanism of cancer cell cytotoxicity after near-infrared photoimmunotherapy. ACS Cent Sci 2018;4(11):1559-69.
DOI: 10.1021/acscentsci.8b00565
Kitamura N, Sento S, Yoshizawa Y, et al. Current trends and future prospects of molecular targeted therapy in head and neck squamous cell carcinoma. Int J Mol Sci 2020;22(1):240.
DOI: 10.3390/ijms22010240
Cognetti DM, Johnson JM, Curry JM, et al. RPhase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma. Head Neck 2021;43(12):3875-87.
DOI: 10.1002/hed.26885
Boreddy SR, Nair R, Pandei PK, et al. BCA101 Is a Tumor-Targeted Bifunctional Fusion Antibody That Simultaneously Inhibits EGFR and TGFβ Signaling to Durably Suppress Tumor Growth. Cancer Res 2023;83(11):1883-904.
DOI: 10.1158/0008-5472.CAN-21-4425
Hanna GJ, Kaczmar JM, Zandberg DP, et al. Dose expansion results of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma. ESMO Congress 2023.
DOI: 10.1016/j.annonc.2023.09.2066
Xue J, Kong D, Yao Y, et al. Prediction of Human Pharmacokinetics and Clinical Effective Dose of SI-B001, an EGFR/HER3 Bi-specific Monoclonal Antibody. J Pharm Sci 2020;109(10):3172-80.
DOI: 10.1016/j.xphs.2020.06.015
Xue L, Yang K, Fang M, et al. Results from two phase II studies of SI-B001, an EGFR×HER3 bispecific antibody with/without chemotherapy in patients (pts) with recurrent and metastatic headand neck squamous cell carcinoma (HNSCC). ASCO Congress 2023.
DOI: 10.1200/JCO.2023.41.16_suppl.6037
Bauman JE, Saba NF, Roe D, et al. Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer. J Clin Oncol 2023;41(22):3851-62.
DOI: 10.1200/JCO.22.01994
Wang J, Yao X, Huang J. New tricks for human farnesyltransferase inhibitor: cancer and beyond. Medchemcomm 2017;8(5):841-54.
DOI: 10.1039/C7MD00030H
Mountzios G, Rampias T, Psyrri A, et al. The mutational spectrum of squamous-cell carcinoma of the head and neck: Targetable genetic events and clinical impact. Ann Oncol 2014;25:1889-900.
DOI: 10.1093/annonc/mdu143
Leemans CR, Snijders PJF, Brakenhoff RH. The molecular landscape of head and neck cancer. Nat Rev Cancer 2018;18(5):269-82.
DOI: 10.1038/nrc.2018.11
Ho AL, Brana I, Haddad R, et al. Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations J Clin Oncol 2021;39(17):1856-64.
DOI: 10.1200/JCO.20.02903
Ho AL Adkins D, Hanna GJ, et al. A phase 2 study evaluating tipifarnib in m HRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM HN). ESMO Congress 2023.
DOI: 10.1016/j.annonc.2023.10.041
Gui L, He X, Yang J, et al. Pembrolizumab plus Anlotinib as first line treatment in patients of CPS≥1 with recurrent or metastatic head and neck squamous cell carcinoma: A prospective phase II study. ESMO Asia Congress 2022.
DOI: 10.1016/j.annonc.2022.10.265
Shi Y, Gao L, Tian Y, et al. Penpulimab combined with anlotinib in patients with R/M HNSCC after failure of platinum-based chemotherapy: a single-arm, multicenter, phase II study. ESMO Open 2023;8(6):102194.
DOI: 10.1016/j.esmoop.2023.102194
Li YL, Zhao H, Ren XB. Relationship of VEGF/VEGFR with immune and cancer cells: staggering or forward? Cancer Biol Med 2016;13(2):206-14.
DOI: 10.20892/j.issn.2095-3941.2015.0070
Saba NF, Steuer C, Ekpenyong A, et al. Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial. Nat Med 2023;29(4):880-7.
DOI: 10.1038/s41591-023-02275-x

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