Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 16, 2023

Abstract Head and neck cancer (HNC) is malignant, genetically complex difficult to treat the sixth most frequent cancer, with tobacco, alcohol human papillomavirus being major risk factors. Based on epigenetic data, HNC remarkably heterogeneous, treatment remains challenging. There a lack of significant improvement in survival quality life patients HNC. Over half experience locoregional recurrence or distal metastasis despite current multiple traditional therapeutic strategies immunotherapy. In addition, resistance chemotherapy, radiotherapy some targeted therapies common. Therefore, it urgent explore more effective tolerable improve clinical outcomes patients. Recent therapy studies have focused identifying promising biomarkers developing therapies. A well understanding pathogenesis contributes learning about its inner association, which provides novel insight into development small molecule inhibitors. this review, we summarized vital signaling pathways discussed potential targets against critical molecules HNC, as presenting preclinical animal models ongoing completed therapy, may contribute favorable prognosis Targeted combination other limitations were also discussed.

Язык: Английский

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Immunotherapy and Biomarker Testing in Recurrent and Metastatic Head and Neck Cancers: ASCO Guideline

Journal of Clinical Oncology, Год журнала: 2022, Номер 41(5), С. 1132 - 1146

Опубликована: Дек. 15, 2022

To provide evidence-based recommendations for practicing physicians and other health care providers on immunotherapy biomarker testing head neck cancers.ASCO convened an Expert Panel of medical oncology, surgical radiation radiology, pathology, patient advocacy experts to conduct a literature search, including systematic reviews, meta-analyses, randomized controlled trials, prospective retrospective comparative observational studies published from 2000 through 2022. Outcomes interest included survival, overall response, locoregional control. members used available evidence informal consensus develop guideline recommendations.The search identified 28 relevant inform the base this guideline.When possible, were developed address testing, first-line treatment regimens based programmed death ligand-1 scores, in platinum-refractory recurrent or metastatic squamous cell carcinoma, nasopharyngeal therapy combination with local recurrence.Additional information is at www.asco.org/head-neck-cancer-guidelines.

Язык: Английский

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Analytical Validation of NavDx, a cfDNA-Based Fragmentomic Profiling Assay for HPV-Driven Cancers

Diagnostics, Год журнала: 2023, Номер 13(4), С. 725 - 725

Опубликована: Фев. 14, 2023

The NavDx® blood test analyzes tumor tissue modified viral (TTMV)-HPV DNA to provide a reliable means of detecting and monitoring HPV-driven cancers. has been clinically validated in large number independent studies integrated into clinical practice by over 1000 healthcare providers at 400 medical sites the US. This Clinical Laboratory Improvement Amendments (CLIA), high complexity laboratory developed test, also accredited College American Pathologists (CAP) New York State Department Health. Here, we report detailed analytical validation NavDx assay, including sample stability, specificity as measured limits blank (LOBs), sensitivity illustrated via detection quantitation (LODs LOQs). LOBs were 0-0.32 copies/μL, LODs 0-1.10 LOQs <1.20-4.11 demonstrating data provided NavDx. In-depth evaluations accuracy intra- inter-assay precision shown be well within acceptable ranges. Regression analysis revealed degree correlation between expected effective concentrations, excellent linearity (R2 = 1) across broad range analyte concentrations. These results demonstrate that accurately reproducibly detects circulating TTMV-HPV DNA, which aid diagnosis surveillance

Язык: Английский

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Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 14, 2023

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate safety and activity camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) PD-1 inhibitor resistant NPC 2, NCT04548271). Here we report on primary outcome objective response rate (ORR) secondary endpoints safety, duration response, disease control rate, progression-free survival, overall survival. The endpoint ORR was met cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) (34.3%; 17.0-51.8, 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported 47 (65.3%) 72 patients. Results our predefined exploratory investigation predictive biomarkers show: B cell markers are most differentially expressed genes tumors responders versus non-responders that tertiary lymphoid structure is associated higher ORR; Angiogenesis gene expression signatures strongly 2. Camrelizumab combination effectiveness high PD-L1, VEGF Receptor B-cell-related signatures. shows promising efficacy measurable profile RM-NPC

Язык: Английский

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Multimodality treatment in recurrent/metastatic squamous cell carcinoma of head and neck: current therapy, challenges, and future perspectives

Frontiers in Oncology, Год журнала: 2024, Номер 13

Опубликована: Янв. 4, 2024

Squamous cell carcinoma of the head and neck is a complex group diseases that presents challenge to clinician. The prognosis in recurrent/metastatic disease particularly dismal, with median survival approximately 12 months. Recently, personalized multimodal approach has increased by integrating locoregional strategies (salvage surgery stereotactic radiotherapy) systemic treatments (chemotherapy, immunotherapy, target therapy). Malnutrition significant clinical problem interferes dose intensity, thus, feeding supplementation critical not only increase quality life but also improve overall survival. With this review, we want emphasize importance multidisciplinary approach, life, nutritional supportive care integrate latest updates predictive biomarkers for immunotherapy future therapeutic strategies.

Язык: Английский

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Cyclic increase in the histamine receptor H1-ADAM9-Snail/Slug axis as a potential therapeutic target for EMT-mediated progression of oral squamous cell carcinoma

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 20, 2025

Abstract The intricate involvement of the histaminergic system, encompassing histamine and receptors, in progression diverse neoplasias has attracted considerable scrutiny. Histamine receptor H1 (HRH1) was reported to be overexpressed several cancer types, but its specific functional implications oral squamous cell carcinoma (OSCC) predominantly remain unexplored. Our findings indicate that dysregulated high levels HRH1 were correlated with lymph node (LN) metastasis poor prognoses OSCC patients. We identified a disintegrin metalloprotease 9 (ADAM9) as critical downstream target HRH1, promoting protumorigenic prometastatic characteristics both vitro vivo. Molecular investigations revealed cyclic increase HRH1-ADAM9-Snail/Slug axis promoted epithelial-to-mesenchymal transition (EMT). Clinical analyses demonstrated significant correlations expression ADAM9 EMT-related markers, elevated also associated LN Regarding therapeutic aspects, we discovered activated STAT3 acts compensatory pathway for long-term signaling blockade cells. Combining inhibition using their respective inhibitors or short hairpin (sh)RNAs enhanced tumor-suppressive effects compared inhibition/depletion alone cells xenograft model. In summary, emerged valuable biomarker predicting progression, combined targeting may represent promising strategy preventing progression.

Язык: Английский

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Combination Therapy as a Promising Way to Fight Oral Cancer

Pharmaceutics, Год журнала: 2023, Номер 15(6), С. 1653 - 1653

Опубликована: Июнь 4, 2023

Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, radiation therapy, alone or in combination, are associated significant side effects. Currently, combination therapy has become the standard practice for of locally advanced oral cancer, emerging an effective approach improving outcomes. In this review, we present in-depth analysis current advancements therapies cancer. The review explores therapeutic options highlights limitations monotherapy approaches. It then focuses on combinatorial approaches target microtubules, well various signaling pathway components implicated progression, namely, DNA repair players, epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, immune checkpoint proteins. discusses rationale behind combining different agents examines preclinical clinical evidence supporting effectiveness these combinations, emphasizing their ability enhance response overcome drug resistance. Challenges discussed, including potential toxicity need personalized A future perspective also provided highlight existing challenges possible resolutions toward translation therapies.

Язык: Английский

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Circulating Tumor HPV DNA for Surveillance of HPV-Positive Oropharyngeal Squamous Cell Carcinoma

JAMA Oncology, Год журнала: 2023, Номер 9(12), С. 1716 - 1716

Опубликована: Окт. 12, 2023

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection recurrent are imperfect. There is growing interest in improving through the use plasma-based assays able to detect circulating tumor HPV DNA.Although most DNA remain research domain, tissue-modified viral assay became commercially available United States early 2020 and been increasingly used clinical setting. With rapidly increasing incidence HPV-positive concomitant expansion biomarker capabilities this disease, it critical reexamine current posttreatment practices determine whether emerging technologies may be improve outcomes survivor population. However, caution advised; not known biomarker-based truly beneficial, as true with any intervention, capacity cause harm.Using Margaret Pepe's classic 5 phases development cancer framework, article reviews state knowledge, highlights existing knowledge gaps, suggests that should prioritized understand association between patient outcomes. Specific attention paid assay, given its use. This review serve road map future guide clinicians considering adoption practice. Enrollment into trials incorporating prioritized.

Язык: Английский

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Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab – the randomized phase 2 FOCUS trial

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 7, 2024

Background Globally, head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignancy. Despite aggressive multimodal treatment approaches, recurrent and/or metastatic (R/M) disease develops in &gt;50% of patients. In this setting, pembrolizumab was approved for patients with PD-L1 expression. However, response rates checkpoint inhibitor monotherapy remain limited strategies to strengthen tumor-directed immune responses are needed. Objective The FOCUS trial designed estimate effectiveness UV1 vaccination combination versus as a single agent R/M HNSCC. Methods analysis two-armed, randomized, multicenter phase II study which evaluate efficacy feasibility hTERT-targeted cancer vaccine add-on 1st line positive (combined score ≥1) Secondary objectives exploration patient subgroups likely deriving benefit from novel establishment liquid biopsy tumor monitoring Ethics dissemination This clinical will be conducted compliance Good Clinical Practice accordance Declaration Helsinki. It intended publish results peer-reviewed scientific journals present its content at academic conferences. Conclusions A significant number HNSCC frail may not tolerate chemotherapy, these only suitable monotherapy. long term stabilizations exception there need development efficacious regimens population. aims optimize promising new approach. Trial Registration https://clinicaltrials.gov/study/NCT05075122 , identifier NCT05075122.

Язык: Английский

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Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment

Cancer Letters, Год журнала: 2024, Номер 598, С. 217095 - 217095

Опубликована: Июль 2, 2024

Язык: Английский

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