Targeted Therapies and Immunotherapies in the Treatment of Esophageal Cancers

Barsouk, Adam; Rawla, Prashanth; Hadjinicolaou, Andreas V.; Aluru, John Sukumar; Barsouk, Alexander

doi:10.3390/medsci7100100

Cited by 29 publications

(35 citation statements)

References 61 publications

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“…Patients showing disease progression upon standard therapies should be subjected to genomic profiling and considered for clinical trials aimed at testing targeted therapies. Furthermore, it was shown in a recent report that Pembrolizumab can be used as a treatment option for PD-L1-positive patients with an already advanced tumor stage and Trastuzumab has been approved as first-line treatment in combination with chemotherapy for HER2/neu-positive patients [ 69 ]. Future targeted therapies may include CDK4/6 inhibitors, PARP inhibitors and inhibitors targeting the NRF2 and Wnt signaling pathways [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients

Richter

Baratay

Röder

et al. 2020

JCM

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Hematogenic tumor cell spread is a key event in metastasis. However, the clinical significance of circulating tumor cells (CTC) in the blood and disseminated tumor cells (DTC) in bone marrow is still not fully understood. Here, the presence of DTC and CTC in esophageal cancer (EC) patients and its correlation with clinical parameters was investigated to evaluate the CTC/DTC prognostic value in EC. This study included 77 EC patients with complete surgical tumor resection. CTC and DTC were analyzed in blood and bone marrow using nested CK20 reverse transcription-nested polymerase chain reaction (RT-PCR) and findings were correlated with clinical data. Twenty-seven of 76 patients (36.5%) showed CK20 positivity in the blood, 19 of 61 patients (31.1%) in bone marrow, and 40 (51.9%) of 77 patients were positive in either blood or bone marrow or both. In multivariate analyses, only the DTC status emerged as independent predictor of overall and tumor specific survival. Our study revealed that, while the presence of CTC in blood is not associated with a worse prognosis, DTC detection in the bone marrow is a highly specific and independent prognostic marker in EC patients. Larger cohort studies could unravel how this finding can be translated into improved therapy management in EC.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients

Richter

Baratay

Röder

et al. 2020

JCM

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“…The molecular characterization of EAC is divided into four etiological/genetic subtypes based on gastric adenocarcinoma molecular characterization classification ( Cancer Genome Atlas Research Network, 2014 ): (1) EBV-associated tumors; (2) Microsatellite instability (MSI) tumors commonly with PIK3CA, EGFR and human epidermal growth factor receptor 2 (HER2) mutations; (3) Genomically stable tumors, (4) Chromosomally instability (CIN) tumors with TP53 mutations as well as RTK/RAS, VEGFR, and p110 amplifications ( Barsouk et al, 2019 ). In these genomic subtypes, the MSI-high and EBV subtypes have shown great responsiveness to immune checkpoint inhibitors (ICIs), such as pembrolizumab ( Kim et al, 2018 ; Le et al, 2018 ; Shitara et al, 2018 ).…”

Section: Molecular Targeted Therapymentioning

confidence: 99%

Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer

Mao

Zeng

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Pharmaceutical therapies are essential for esophageal cancer (EC). For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. For the unresectable, recurrent, and metastatic EC, the pharmaceutical therapy is the limited effective regimen to alleviate the disease and prolong the progression-free survival and overall survival. In this review, we focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The chemotherapy regimen is based on cytotoxic agents such as platinum-based complexes, fluorinated pyrimidines and taxenes. Although the cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The targeted molecular therapy is an essential supplement for chemotherapy; however, there are only a few targeted therapies available in clinical practice. Trastuzumab and ramucirumab are the only two molecular therapy drugs which are approved by the US Food and Drug Administration to treat advanced and/or metastatic EC. Although the targeted therapy usually achieves effective benefits in the early stage therapy of EC, the patients will always develop drug resistance during treatment. ICIs have had a significant impact on routine clinical practice in cancer treatment. The anti-programmed cell death-1 monoclonal antibodies pembrolizumab and nivolumab, as the ICIs, are recommended for advanced EC by several clinical trials. However, the significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment.

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“…4 The current standard treatments of EC mainly include chemoradiotherapy, surgery, and endoscopic resection. 5 Although the Food and Drug Administration (FDA) has approved some targeted drugs such as programmed cell death protein 1 (PD-1) inhibitors, human epidermal growth factor receptor-2 (HER2), and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies for the treatment of EC, the survival rate of most patients with advanced EC is still low, 6 which requires us to conduct a more systematic evaluation of the exact molecular pathogenesis of EC in order to develop novel biomarkers and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

<p>Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche</p>

Han¹,

Cao²,

Huang³

et al. 2020

CMAR

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Esophageal cancer (EC) is the sixth most deadly cancer, and its incidence is still increasing year by year. Although the researches on the molecular mechanisms of EC have been widely carried out and incremental progress has been made, its overall survival rate is still low. There is cumulative evidence showing that the esophageal microenvironment plays a vital role in the development of EC. In precancerous lesions of the esophagus, high-risk environmental factors can promote the development of precancerous lesions by inducing the production of inflammatory factors and the recruitment of immune cells. In the tumor microenvironment, tumor-promoting cells can inhibit anti-tumor immunity and promote tumor progression through a variety of pathways, such as bone marrow-derived suppressor cells (MDSCs), tumor-associated fibroblasts (CAFs), and regulatory T cells (Tregs). The formation of extracellular hypoxia and acidic microenvironment and the change of extracellular matrix stiffness are also important factors affecting tumor progression and metastasis. Simultaneously, primary tumor-derived cytokines and bone marrow-derived immune cells can also promote the formation of pre-metastasis niche of EC lymph nodes, which are beneficial to EC lymph node metastasis. Further research on the specific mechanism of these processes in the occurrence, development, and metastasis of each EC subtype will support us to grasp the overall pre-cancerous prevention, targeted treatment, and metastatic assessment of EC.

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Targeted Therapies and Immunotherapies in the Treatment of Esophageal Cancers

Cited by 29 publications

References 61 publications

Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients

Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients

Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer

<p>Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche</p>

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