Differential modulation of PI3K/Akt/mTOR activity by EGFR inhibitors: A rationale for co-targeting EGFR and PI3K in cisplatin-resistant HNSCC.

Purpose: To find a new strategy to treat cisplatin-resistant head and neck squamous cell carcinoma (HNSCC), we investigated the effects of EGFR inhibitors on the PI3K/Akt/mTOR pathway and determined the efficacy of EGFR inhibitors in combination with PI3K inhibitors to suppress cell proliferation in cisplatin-resistant-HNSCC.

Methods: The cisplatin-resistant HNSCC cell lines were treated with four FDA approved EGFR inhibitors, which included Gefitinb or Erlotinib alone, or in combination with the pan-PI3K inhibitor, BKM120. Phosphorylation and total protein levels of cells were assessed by Western blot analysis.

Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy.

Objectives: We sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT).

Materials And Methods: Patients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.

Regionalization of Head and Neck Oncology Tumor Boards: Perspectives of Collaborating Physicians.

Objectives: To survey academic and community physician preferences regarding the virtual multidisciplinary tumor board (MTB) for further improvement and expansion.

Study Design: This anonymous 14-question survey was sent to individuals that participated in the head and neck virtual MTBs. The survey was sent via email beginning August 3, 2021, through October 5, 2021.

Gross tumor volume margin and local control in p16-positive oropharynx cancer patients treated with intensity modulated proton therapy.

Background: To determine if the extent of high-dose gross tumor volume (GTV) to clinical target volume (CTV) expansion is associated with local control in patients with p16-positive oropharynx cancer (p16+ OPC) treated with definitive intensity modulated proton therapy (IMPT).

Methods: We performed a retrospective analysis of patients with p16+ OPC treated with IMPT at a single institution between 2016 and 2021. Patients with a pre-treatment PET-CT and restaging PET-CT within 4 months following completion of IMPT were analyzed.

Simultaneously targeting ErbB family kinases and PI3K in HPV-positive head and neck squamous cell carcinoma.

Objectives: To identify the most effective PI3K and EGFR inhibitors in HPV-positive head and neck squamous cell carcinoma (HNSCC) and investigate the efficacy of a combination of an ErbB family kinase inhibitor and a PI3K inhibitor to inhibit cell proliferation of HPV-positive HNSCC.

Materials And Method: HPV-positive HNSCC cell lines were treated with the FDA approved ErbB kinase inhibitor, Afatinib or FDA-approved PI3K inhibitor, Copanlisib, alone or in combination, and phosphorylation and total protein levels of cells were assessed by Western blot analysis.Cell proliferation and apoptosis were examined by MTS assay, flow cytometry, and Western blots, respectively.

Cost-effectiveness of concurrent radiation with cetuximab or chemotherapy in older patients with oropharyngeal cancer.

To assess the cost-effectiveness of definitive therapies for nonmetastatic oropharyngeal cancer (OPC). Using the Surveillance, Epidemiology and End Results-Medicare dataset, patients diagnosed between 2000 and 2011 were identified. The cost-effectiveness of chemoradiation (CRT) versus radiotherapy (RT), cetuximab plus RT (cetuximab-RT) versus RT and cetuximab-RT versus CRT were estimated.

Targeting Wee1 kinase to suppress proliferation and survival of cisplatin-resistant head and neck squamous cell carcinoma.

Purpose: We investigated the role of Wee1 kinase in cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) in multiple cisplatin-resistant HNSCC cell lines and determined the efficacy of either Wee1 inhibitor, AZD1775 alone, or in combination with cisplatin, on cisplatin-resistant HNSCC inhibition.

Methods: Phosphorylation and total protein levels of cells were assessed by Western blot analysis. Cell viability and apoptosis were examined by MTS assay and flow cytometry, respectively.

Comparison of efficacy and toxicity of chemoradiation regimens for head and neck squamous cell carcinoma primary treatment.

Background: The best chemoradiation regimen to treat locally and regionally advanced head and neck squamous cell carcinoma (HNSCC) is yet to be established.

Methods: We compared overall survival (OS) and adverse events following chemoradiation regimens (high-dose [HDC] or low-dose [LDC] cisplatin, or carboplatin [CB]) in HNSCC cases selected from SEER-Medicare linked database.

Results: Of the 1335 cases who underwent radiotherapy, 264 received HDC, 259 received LDC, and 353 received CB, concurrently.

Evaluating the Jaccard Similarity Index as a Persistence Measure of Multiple Anal Human Papillomavirus Among Nigerian Men Who Have Sex With Men.

Background: Multiple anal human papillomavirus (HPVs) may increase the risk of anal cancer among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). The Jaccard Similarity Index (JSI) was explored as a measure of multiple HPV persistence.

Methods: The TRUST/RV368 cohort enrolled MSM living with and without HIV in Abuja and Lagos, Nigeria.

Treatment modalities, adverse events, and survival outcomes in older patients with head and neck squamous cell carcinoma.

Background: Chemoradiation with curative intent in older adults with locally advanced head and neck squamous cell carcinoma (HNSCC) has been a challenge, because of its potential toxicities.

Methods: We selected primary HNSCC cases from the SEER-Medicare linked database, assessed overall survival (OS) and adverse events and their associations with different treatments, across four age groups including the youngest (66-69 years) and the oldest (≥80 years).

Results: Better OS was associated with chemoradiation compared to radiation alone, not only in all patients (N = 5879) (hazard ratio [HR] = 0.

Impact of the Novel Coronavirus 2019 (COVID-19) Pandemic on Head and Neck Cancer Care.

Objective: The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on head and neck oncologic care at a tertiary care facility.

Study Design: This was a cross-sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period.

Adherence to Guideline-Concordant Care and Its Effect on Survival in Black Patients with Head and Neck Cancers: A SEER-Medicare Analysis.

Background: In head and neck squamous cell carcinoma (HNSCC), Black patients continue to have worse survival when compared with White patients. The cause of this disparity is multifaceted and cannot be explained by one etiology alone. To investigate this disparity, we used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine adherence to guideline-concordant care (GCC) as defined by the National Comprehensive Cancer Network.

Multiple HPV infections among men who have sex with men engaged in anal cancer screening in Abuja, Nigeria.

Background: Anal precancers and cancers can be detected during screening with high-resolution anoscopy (HRA). The sensitivity of HRA depends on the burden and duration of human papillomavirus (HPV) among those screened as well as anoscopist proficiency, which is highly correlated with prior screening experience. Our objective was to compare the identification and type of HPV and the likelihood of HRA-detected precancer for men who have sex with men (MSM) undergoing their first HRA-screening in Nigeria.

Inhibition of IKKβ/NF-κB signaling pathway to improve Dasatinib efficacy in suppression of cisplatin-resistant head and neck squamous cell carcinoma.

Proto-oncogene tyrosine-protein kinase Src plays an important role in Head and Neck Squamous Cell Carcinoma (HNSCC). However, the FDA-approved SRC inhibitor Dasatinib shows very limited efficacy in HNSCC clinical trials, even though Dasatinib can completely inhibit SRC in the laboratory setting. These results suggest that SRC inhibition can cause compensatory up-regulation and/or activation of other survival pathways, which suggests that co-targeting of SRC and the potential signaling pathways may improve the Dasatinib efficacy.

Satisfaction with high-resolution anoscopy for anal cancer screening among men who have sex with men: a cross-sectional survey in Abuja, Nigeria.

Background: Men who have sex with men (MSM) living with HIV are at increased risk for anal cancer. We evaluated satisfaction with first-time anal cancer screening using high resolution anoscopy (HRA) as a cross sectional survey among men who have sex with men (MSM) attending a community-engaged clinic in Abuja, Nigeria.

Methods: Between March and August 2017, 342 MSM underwent screening and 307 (89%) completed a satisfaction survey that evaluated 8 domains related to expectations, convenience, staff interpersonal skills, physical surroundings, technical competence, pain/discomfort, general satisfaction, and intention to re-screen if symptomatic.

Suppression of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma through IKKβ inhibition.

We explored the role of the transcription factor, NF-κB, and its upstream kinase IKKβ in regulation of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We showed that cisplatin-resistant HNSCC cells have a stronger ability to migrate and invade, as well as display higher IKKβ/NF-κB activity compared to their parental partners. Importantly, we found that knockdown of IKKβ, but not NF-κB, dramatically impaired cell migration and invasion in these cells.

A Translational Approach to Cancer Research, Education and Training.

The demand for biomedical researchers and health science professionals has increased over the past several decades. This need is particularly acute in the fields of cancer research and oncology in which technological advances have fueled an unprecedented pace of laboratory discoveries and their applications in novel diagnostic and therapeutic strategies. Internships that expose undergraduate students to cancer research and patient care serve an important function in meeting this need by educating trainees about careers in this field and inspiring them to pursue these professional paths.

Conditional Reprogramming for Patient-Derived Cancer Models and Next-Generation Living Biobanks.

Traditional cancer models including cell lines and animal models have limited applications in both basic and clinical cancer research. Genomics-based precision oncology only help 2-20% patients with solid cancer. Functional diagnostics and patient-derived cancer models are needed for precision cancer biology.

Implementation of and Early Outcomes From Anal Cancer Screening at a Community-Engaged Health Care Facility Providing Care to Nigerian Men Who Have Sex With Men.

Purpose: Anal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria.

Methods: From August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort.

Inhibition of cisplatin-resistant head and neck squamous cell carcinoma by combination of Afatinib with PD0325901, a MEK inhibitor.

ErbB family members that contain EGFR, HER2, HER3 and HER4 play important roles in many cancer types, including head and neck; however, inhibition of these receptors by small molecule kinase inhibitors showed limited results due to compensatory up-regulation of some key survival signaling pathways. Here, we explore the effectiveness of Afatinib, an irreversible inhibitor of EGFR, HER2, and HER4, in combination with the MEK inhibitor PD0325901 to inhibit cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We treated two cisplatin-resistant HNSCC cell lines, UMSCC74B and O28, with Afatinib, PD0325901, or a combination, and measured signaling pathways, cell proliferation, and survival.

Regulation of cisplatin-resistant head and neck squamous cell carcinoma by the SRC/ETS-1 signaling pathway.

Background: We investigated the role of the ETS-1 transcription factor in Head and Neck Squamous Cell Carcinoma (HNSCC) in multiple cisplatin-resistant HNSCC cell lines.

Methods: We examined its molecular link with SRC and MEK/ERK pathways and determined the efficacy of either MEK/ERK inhibitor PD0325901 or SRC inhibitor Dasatinib on cisplatin-resistant HNSCC inhibition.

Results: We found that ETS-1 protein expression levels in a majority of cisplatin-resistant HNSCC cell types were higher than those in their parental cisplatin sensitive partners.

The American Cancer Society 2035 challenge goal on cancer mortality reduction.

A summary evaluation of the 2015 American Cancer Society (ACS) challenge goal showed that overall US mortality from all cancers combined declined 26% over the period from 1990 to 2015. Recent research suggests that US cancer mortality can still be lowered considerably by applying known interventions broadly and equitably. The ACS Board of Directors, therefore, commissioned ACS researchers to determine challenge goals for reductions in cancer mortality by 2035.

Minimizing the burden of cancer in the United States: Goals for a high-performing health care system.

Between 1991 and 2015, the cancer mortality rate declined dramatically in the United States, reflecting improvements in cancer prevention, screening, treatment, and survivorship care. However, cancer outcomes in the United States vary substantially between populations defined by race/ethnicity, socioeconomic status, health insurance coverage, and geographic area of residence. Many potentially preventable cancer deaths occur in individuals who did not receive effective cancer prevention, screening, treatment, or survivorship care.

Co-targeting EGFR and IKKβ/NF-κB signalling pathways in head and neck squamous cell carcinoma: a potential novel therapy for head and neck squamous cell cancer.

Background: Epidermal growth factor receptor (EGFR) plays an important role in head and neck squamous cell carcinoma (HNSCC) proliferation and therapy resistance, but the efficacy of targeting of EGFR for therapy has been limited. Here, we explore the molecular link between EGFR and inhibitor of κB kinase β/nuclear factor-κB (IKKβ/NF-κB) signalling pathways in the regulation of HNSCC EGFR inhibitor resistance.

Methods: We performed in vitro experiments in eight human HNSCC cell lines and a patient-derived HNSCC cell line as well as in vivo xenografts in a human HNSCC cell line.

Definitive radiation with concurrent cetuximab vs. radiation with or without concurrent cytotoxic chemotherapy in older patients with squamous cell carcinoma of the head and neck: Analysis of the SEER-medicare linked database.

Objective: To evaluate OS and toxicity after definitive radiation with concurrent cetuximab (CTX-RT) compared to radiation with concurrent cytotoxic chemotherapy (CRT) in older HNSCC patients via the SEER-Medicare linked database.

Materials And Methods: We used the SEER-Medicare linked database to evaluate OS in HNSCC patients (Oropharynx, Larynx, Hypopharynx, Nasopharynx) diagnosed over 2005-2011, following FDA approval of cetuximab in combination with radiation therapy (RT) in March 2006.

Results: 2135 beneficiaries were identified.