scholarly journals Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy

2021 ◽  
Vol 13 ◽  
pp. 175883592094941
Author(s):  
Morena Fasano ◽  
Carminia Maria Della Corte ◽  
Giuseppe Viscardi ◽  
Raimondo Di Liello ◽  
Fernando Paragliola ◽  
...  
Keyword(s):  
Head And Neck ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Treatment Options ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Clinical Settings ◽  
Histologic Subtype ◽  
Targeted Agent

Head and neck cancers (HNC) represent the seventh most frequent cancer worldwide, with squamous cell carcinomas as the most frequent histologic subtype. Standard treatment for early stage diseases is represented by single modality surgery or radiotherapy, whereas in the locally advanced and recurrent or metastatic settings a more aggressive multi-modal approach is needed with locoregional intervention and/or systemic therapies. Epidermal Growth Factor Receptor (EGFR) plays an important role in HNC biology and has been studied extensively in preclinical and clinical settings. In this scenario, anti-EGFR targeted agent cetuximab, introduced in clinical practice a decade ago, represents the only approved targeted therapy to date, while the development of immune-checkpoint inhibitors has recently changed the available treatment options. In this review, we focus on the current role of anti-EGFR therapies in HNCs, underlying available clinical data and mechanisms of resistance, and highlight future perspectives regarding their role in the era of immunotherapy.

Advances in Treatment Options for Patients with Pancreatic Cancer

2009 ◽  
Vol 05 (01) ◽  
pp. 72
Author(s):  
Carole Harris ◽  
David Goldstein ◽  
◽  
Keyword(s):  
Treatment Options ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Term Survival ◽  
Impact On Survival ◽  
Epidermal Growth ◽  
Basic Biology

Pancreatic carcinoma continues to be a problematic malignancy characterized by poor long-term survival, late diagnosis, and resistance to systemic therapy. Nevertheless, meaningful advances in treatment have occurred. These include the use of gemcitabine chemotherapy alone and in combination, the identification of active second-line therapy, and the emergence of epidermal growth factor receptor (EGFR)-targeted therapy as a new avenue for investigation. The role of radiation in locally advanced disease is promising and will be tested in the phase III setting. Adjuvant therapy has made an important impact on survival and will need to be enhanced with studies of emerging agents. The future will depend on new direction from emerging advances in basic biology.

scholarly journals Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (9) ◽  
pp. 4981
Author(s):  
Teresa Magnes ◽  
Sandro Wagner ◽  
Dominik Kiem ◽  
Lukas Weiss ◽  
Gabriel Rinnerthaler ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Upper Aerodigestive Tract ◽  
Hpv Status

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials.

scholarly journals How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies

ESMO Open ◽  
2018 ◽  
Vol 3 (Suppl 1) ◽  
pp. e000357 ◽  
Author(s):  
Ji Hyun Park ◽  
Jin-Hee Ahn ◽  
Sung-Bae Kim
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Tumour Microenvironment ◽  
Therapeutic Benefit ◽  
Current Standard

Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the ‘BRCAness’ highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors. However, regardless of enriched chemosensitivity and immunogenicity, majority of patients with TNBC still suffer from dismal clinical outcomes including early relapse and metastatic spread. Therefore, efforts into more precise and personalised treatment are critical at this point. Accordingly, the advance of multiomics has revealed novel actionable targets including PI3K-Akt-mTOR and epidermal growth factor receptor signalling pathways, which might actively participate in modulating the chemosensitivity and immune system. Also, TNBC has long been considered a potential protagonist of immunotherapy in breast cancer, supported by abundant tumour-infiltrating lymphocytes and heterogeneous tumour microenvironment. Despite that, earlier studies showed somewhat unsatisfactory results of monotherapy with immune-checkpoint inhibitors, consistently durable responses in responders were noteworthy. Based on these results, further combinatorial trials either with other chemotherapy or targeted agents are underway. Incorporating immune-molecular targets into combination as well as refining the standard chemotherapy might be the key to unlock the future of TNBC. In this review, we share the current and upcoming treatment options of TNBC in the framework of scientific and clinical data, especially focusing on early stage of TNBC.

scholarly journals The Role of Immunotherapy to Overcome Resistance in Viral-Associated Head and Neck Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Rebecca R. Pharaon ◽  
Yan Xing ◽  
Mark Agulnik ◽  
Victoria M. Villaflor
Keyword(s):  
Head And Neck ◽  
Cellular Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Head And Neck Cancers ◽  
Adoptive Cellular Therapy ◽  
Barr Virus ◽  
Epstein Barr

A subset of head and neck cancers arising in the oropharynx and the nasopharynx are associated with human papillomavirus or Epstein–Barr virus. Unfortunately, limited treatment options exist once patients develop recurrent or metastatic disease in these cancers. Interest has risen in utilizing novel strategies including combination immune checkpoint inhibitors, vaccines, and adoptive cellular therapy, to improve treatment response and outcomes. Several ongoing studies are investigating the potential to overcome resistance to standard of care chemoradiation therapy with monotherapy or combination immunotherapy strategies in these viral-associated head and neck cancers.

scholarly journals The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Cirrhosis ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Serum Samples ◽  
Disease Etiology ◽  
Risk Patients ◽  
Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 304
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Javier Molina-Cerrillo ◽  
Teresa Alonso-Gordoa
Keyword(s):  
Adrenocortical Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
Response Efficacy ◽  
Predictors Of Response ◽  
Primary Endpoints ◽  
Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

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