scholarly journals Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance of Head and Neck Cancer: From Basic Research to Clinical Application

2021 ◽  
Vol 8 ◽  
Author(s):  
Xixia Zhang ◽  
Jing Yang
Keyword(s):  
Dna Damage ◽  
Overall Survival ◽  
Head And Neck ◽  
Cancer Cells ◽  
Therapy Monitoring ◽  
Locally Advanced ◽  
Therapeutic Modality ◽  
Current Function ◽  
Non Coding Rnas

Head and neck cancers (HNCs) rank as the sixth common and the seventh leading cause of cancer-related death worldwide, with an estimated incidence of 600,000 cases and 40–50% mortality rate every year. Radiotherapy is a common local therapeutic modality for HNC mainly through the function of ionizing radiation, with approximately 60% of patients treated with radiotherapy or chemoradiotherapy. Although radiotherapy is more advanced and widely used in clinical practice, the 5-year overall survival rates of locally advanced HNCs are still less than 40%. HNC cell resistance to radiotherapy remains one of the major challenges to improve the overall survival in HNC patients. Non-coding RNAs (ncRNAs) are newly discovered functional small RNA molecules that are different from messenger RNAs, which can be translated into a protein. Many previous studies have reported the dysregulation and function of ncRNAs in HNC. Importantly, researchers reported that several ncRNAs were also dysregulated in radiotherapy-sensitive or radiotherapy-resistant HNC tissues compared with the normal cancer tissues. They found that ectopically elevating or knocking down expression of some ncRNAs could significantly influence the response of HNC cancer cells to radiotherapy, indicating that ncRNAs could regulate the sensitivity of cancer cells to radiotherapy. The implying mechanism for ncRNAs in regulating radiotherapy sensitivity may be due to its roles on affecting DNA damage sensation, inducing cell cycle arrest, regulating DNA damage repair, modulating cell apoptosis, etc. Additionally, clinical studies reported that in situ ncRNA expression in HNC tissues may predict the response of radiotherapy, and circulating ncRNA from body liquid serves as minimally invasive therapy-responsive and prognostic biomarkers in HNC. In this review, we aimed to summarize the current function and mechanism of ncRNAs in regulating the sensitivity of HNC cancer cells to radiotherapy and comprehensively described the state of the art on the role of ncRNAs in the prognosis prediction, therapy monitoring, and prediction of response to radiotherapy in HNC.

A phase II study of ARQ 501 in patients with advanced squamous cell carcinoma of the head and neck

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16509-16509 ◽  
Author(s):  
A. Kawecki ◽  
D. R. Adkins ◽  
C. C. Cunningham ◽  
E. Vokes ◽  
D. M. Yagovane ◽  
...  
Keyword(s):  
Dna Damage ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cancer Cells ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Common Adverse Event ◽  
Current Evidence ◽  
Phase 2

16509 Background: ARQ 501 is a DNA damage checkpoint pathway activator whose effect is to induce selective cell death in cancer cells, independent of the tumor cell's p53 status. Current evidence implicates a rapid and sustained increase of the pro-apoptotic protein E2F-1 by ARQ 501 as the mechanism of action. Cancer cells are selectively affected due to their pre-existing DNA damage. In initial clinical trials, there was evidence of activity in some patients with head and neck cancer and pre-clinical investigations also supported this application. Therefore, a phase 2 trial is warranted in this patient population. Methods: A phase 2 study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck who had received up to 3 prior systemic therapies was initiated to assess overall response rate, progression free survival at six months, and to further characterize safety. Cycles consist of four weekly administrations of ARQ 501 at a dose of 450 mg/m2. Dose escalation is allowed if a patient successfully completed a full cycle of therapy and had no related grade 2 adverse events. Results: 59 patients have been enrolled to date and 47 have received at least one infusion of ARQ 501. Data is available for 34 patients (27M / 7F, median age, 57 years). Of the 47 patients treated, 11 patients did not reach a post baseline assessment (2 deaths, 8 PD prior to week 8 and 1 withdrew consent). Although at the current date, most patients have not reached their first tumor evaluation, 5 have been assessed for response per RECIST at eight weeks and one patient is demonstrating stable disease. The drug has been well tolerated with the most common adverse event being anemia (11% ) with corresponding edema, fatigue (both 5%), dyspnea (4%), and hyperbilirubinemia (2%). Conclusions: ARQ 501 is well tolerated in patients with advanced, recurrent or persistent squamous cell carcinoma of the head and neck. Enrollment is ongoing and further results will be presented. No significant financial relationships to disclose.

Emerging role of non-coding RNAs in response of cancer cells to radiotherapy

2021 ◽  
Vol 218 ◽  
pp. 153327
Author(s):  
Kaveh Ebahimzadeh ◽  
Hamed Shoorei ◽  
Seyed Ali Mousavinejad ◽  
Farhad Tondro Anamag ◽  
Marcel E. Dinger ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Non Coding Rnas

The Role of Neck Dissection after Radical Chemoradiation for Locally Advanced Head and Neck Cancer: Should We Move Back

Oncology ◽  
2013 ◽  
Vol 84 (3) ◽  
pp. 174-185 ◽  
Author(s):  
N. Denaro ◽  
E.G. Russi ◽  
G. Numico ◽  
T. Pazzaia ◽  
R. Vitiello ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Dissection ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Advanced Head

Neoadjuvant Chemotherapy Plus Cystectomy Compared With Cystectomy Alone for Locally Advanced Bladder Cancer

2021 ◽  
pp. 141-146
Author(s):  
Vikram M. Narayan
Keyword(s):  
Adverse Effect ◽  
Overall Survival ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Randomized Study ◽  
Locally Advanced ◽  
Common Adverse Effect ◽  
Advanced Bladder Cancer ◽  
Muscle Invasive

This study summarizes a landmark study on the role of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in patients with muscle-invasive bladder cancer. This randomized study of M-VAC plus cystectomy versus cystectomy alone suggested improved overall survival in patients receiving neoadjuvant therapy. Severe granulocytopenia was a common adverse effect in the chemotherapy group, but no deaths were attributed to chemotherapy.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial

2018 ◽  
Vol 36 (11) ◽  
pp. 1064-1072 ◽  
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Jaiprakash Agarwal ◽  
Sarbani Ghosh-Laskar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
Comparable Efficacy ◽  
Advanced Head ◽  
Adjuvant Setting ◽  
Free Survival

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

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