Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

Bauman, Julie E.; Ohr, James; Gooding, William E.; Ferris, Robert L.; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Soloff, Adam C.; Wallweber, Gerald; Winslow, John; Gaither-Davis, Autumn; Grandis, Jennifer R.; Stabile, Laura P.

doi:10.3390/cancers12061537

Cited by 24 publications

(19 citation statements)

References 55 publications

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“…c-Met seems to be a promising biomarker for prognosis in OPSCC and an attractive objective for targeted therapy. Phase 2 trial of humanized monoclonal anti c-Met antibody ficlatuzumab with or without cetuximab in cetuximab resistant recurrent or metastatic HNSCC may be able to show possible effects NCT03422536) [ 74 ]. Unfortunately, the combination of tivantinib (anti c-Met tyrosine kinase inhibitor) and cetuximab was not found to improve the response rate and survival [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Deuß

Gößwein

Gül

et al. 2020

Cancers

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This study aimed to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of human papillomavirus (HPV) status, prognosis and potential relevance for targeted therapy. The protein expression of human epidermal growth factor receptor (Her)1–4 and c-Met were retrospectively assessed using semiquantitative immunohistochemistry on tissue microarrays and analyzed for correlations as well as differences in the clinicopathological criteria. Her1–4 and c-met were overexpressed compared to normal mucosa in 46%, 4%, 17%, 27% and 23%, respectively. Interestingly, most receptors were coexpressed. Her1 and c-Met were inversely correlated with p16 (p = 0.04; p = 0.02). Her2 and c-Met were associated with high tobacco consumption (p = 0.016; p = 0.04). High EGFR, Her3, Her4 and c-Met expression were associated with worse overall and disease-free survival (p ≤ 0.05). Furthermore, EGFR and c-Met expression showed raised hazard ratios of 2.53 (p = 0.02; 95% CI 1.24–5.18) and 2.45 (p = 0.02; 95% CI 1.13–5.35), respectively. Her4 was expressed less in distant metastases than in corresponding primary tumors and was correlated to a higher T category. EGFR and c-Met are relevant negative prognostic factors in OPSCC, independent of known clinicopathological parameters. We suggest dual targeting of EGFR and c-Met as a promising strategy for OPSCC treatment.

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Section: Discussionmentioning

confidence: 99%

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Deuß

Gößwein

Gül

et al. 2020

Cancers

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“…Bauman et al investigated changes in immune signatures in a phase I study of an anti-HGF antibody and an anti-EGFR antibody in patients with cetuximab-resistant, recurrent/ metastatic squamous cell carcinoma. An increase in peripheral T cells, particularly a CD8 + subset, was associated with treatment response (Bauman et al, 2020). Mukherjee et al identified CCL5 as a poor prognostic blood biomarker associated with lower overall survival in patients with advanced pancreatic cancer treated with anti-PD-1.…”

Section: Fsfc Contributions To Cancer Immunotherapy Researchmentioning

confidence: 99%

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Bonilla¹,

Reinin²,

Chua³

2021

Front. Mol. Biosci.

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The Nobel Prize-deserving concept of blocking inhibitory pathways in T cells, to unleash their anti-tumoral capacity, became one of the pillars of cancer treatment in the last decade and has resulted in durable clinical responses for multiple cancer types. Currently, two of the most important goals in cancer immunotherapy are to understand the mechanisms resulting in failure to checkpoint blockade and to identify predictive immunological biomarkers that correlate to treatment response, disease progression or adverse effects. The identification and validation of biomarkers for routine clinical use is not only critical to monitor disease or treatment progression, but also to personalize and develop new therapies. To achieve these goals, powerful research tools are needed. Flow cytometry stands as one of the most successful single-cell analytical tools used to characterize immune cell phenotypes to monitor solid tumors, hematological malignancies, minimal residual disease or metastatic progression. This technology has been fundamental in diagnosis, treatment and translational research in cancer clinical trials. Most recently, the need to evaluate simultaneously more features in each cell has pushed the field to implement more powerful adaptations beyond conventional flow cytometry, including Full Spectrum Flow Cytometry (FSFC). FSFC captures the full emission spectrum of fluorescent molecules using arrays of highly sensitive light detectors, and to date has enabled characterization of 40 parameters in a single sample. We will summarize the contributions of this technology to the advancement of research in immunotherapy studies and discuss best practices to obtain reliable, robust and reproducible FSFC results.

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“…Near limitless throughput and high capture efficiency paired with the ability to distinguish rare cell populations provides a powerful tool for immunophenotyping. Indeed, FSFC has been successfully applied to identify therapy-mediated alterations in peripheral blood mononucleocyte profiles of head and neck squamous cell carcinoma patients ( 252 ).…”

Section: Single-cell Multi-omics Platforms and Their Prospect In Gene And Cell Therapymentioning

confidence: 99%

Exploiting Single-Cell Tools in Gene and Cell Therapy

et al. 2021

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Single-cell molecular tools have been developed at an incredible pace over the last five years as sequencing costs continue to drop and numerous molecular assays have been coupled to sequencing readouts. This rapid period of technological development has facilitated the delineation of individual molecular characteristics including the genome, transcriptome, epigenome, and proteome of individual cells, leading to an unprecedented resolution of the molecular networks governing complex biological systems. The immense power of single-cell molecular screens has been particularly highlighted through work in systems where cellular heterogeneity is a key feature, such as stem cell biology, immunology, and tumor cell biology. Single-cell-omics technologies have already contributed to the identification of novel disease biomarkers, cellular subsets, therapeutic targets and diagnostics, many of which would have been undetectable by bulk sequencing approaches. More recently, efforts to integrate single-cell multi-omics with single cell functional output and/or physical location have been challenging but have led to substantial advances. Perhaps most excitingly, there are emerging opportunities to reach beyond the description of static cellular states with recent advances in modulation of cells through CRISPR technology, in particular with the development of base editors which greatly raises the prospect of cell and gene therapies. In this review, we provide a brief overview of emerging single-cell technologies and discuss current developments in integrating single-cell molecular screens and performing single-cell multi-omics for clinical applications. We also discuss how single-cell molecular assays can be usefully combined with functional data to unpick the mechanism of cellular decision-making. Finally, we reflect upon the introduction of spatial transcriptomics and proteomics, its complementary role with single-cell RNA sequencing (scRNA-seq) and potential application in cellular and gene therapy.

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Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

Cited by 24 publications

References 55 publications

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Exploiting Single-Cell Tools in Gene and Cell Therapy

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