Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma

Curea, F.; Hebbar, Mohamed; Ilie, Silvia; Bacinschi, Xenia; Trifănescu, Oana; Botnariuc, Inga; Anghel, Rodica

doi:10.1089/cbr.2017.2249

Cited by 20 publications

(15 citation statements)

References 122 publications

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“…The preferred regimen for second-line treatment is ramucirumab plus paclitaxel, or ramucirumab monotherapy if the patient is not eligible for paclitaxel (Table S2 in Supplement) [3, 10, 56–58]. A PD-1 inhibitor has recently been approved as third-line or higher therapy for GC/GEJC patients in the US [61].…”

Section: Resultsmentioning

confidence: 99%

Targeted literature review of the global burden of gastric cancer

Casamayor¹,

Morlock²,

Maeda³

et al. 2018

ecancer

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Gastric cancer (GC) and gastroesophageal junction cancers (GEJCs) are the third leading cause of cancer-related death worldwide. Although several studies have evaluated the epidemiology and management of GC and GEJC, to our knowledge, no global estimates of the economic burden of GC and GEJC have yet been reported. This targeted literature review was conducted to summarise the epidemiology and management of GC and GEJC and to estimate its global economic and humanistic burden.The incidence of GC and GEJC is highest in Eastern Asia, several South and Central American countries and Central and Eastern Europe and lowest in North America and Africa. Prognosis is generally poor; the global 5-year survival rate is 5%–10% in advanced stages. Patients with GC and GEJC have more severe symptoms compared with patients with other cancers, and health-related quality of life (HRQoL) worsens as the disease progresses. Given the rapid progression of GC and GEJC at advanced stages, chemotherapy, despite its toxicity, improves HRQoL compared with best supportive care.The costs of GC/GEJC are generally higher than for other cancers; in the US, the average annual cost per patient between 1998 and 2003 was 46,501 USD, compared with 29,609 USD and 35,672 USD for colorectal and lung cancer, respectively. Based on the 2012 incidence data and average costs per patient, estimates of the annual financial burden of GC and GEJC revealed great regional differences. Japan and Iran had the highest (8,492 million USD) and lowest (27 million USD) costs for 2017, respectively, while the estimate for the US was 3,171 million USD. The overall annual cost of GC and GEJC estimated for 2017 in a geographic area including Europe (France, Germany, Italy, Spain and the UK), Asia (Iran, Japan and China), North America (Canada and the US) and Australia was 20.6 billion USD.

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Section: Resultsmentioning

confidence: 99%

Targeted literature review of the global burden of gastric cancer

Casamayor¹,

Morlock²,

Maeda³

et al. 2018

ecancer

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“…In clinical practice, the treatment of gastric and gastroesophageal adenocarcinoma with Lapatinib alone seems to be more challenging compared to its application in breast cancer. Particularly, it seems that it is only suitable for a subset of patients [ 31 , 32 ]. We tested whether Her2 status itself may already influence autophagy under basal conditions.…”

Section: Discussionmentioning

confidence: 99%

Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells

Janser

Adams

Bütler

et al. 2018

IJMS

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Esophageal adenocarcinoma (EAC) is a highly lethal cancer type with an overall poor survival rate. Twenty to thirty percent of EAC overexpress the human epidermal growth factor receptor 2 (Her2), a transmembrane receptor tyrosine kinase promoting cell growth and proliferation. Patients with Her2 overexpressing breast and gastroesophageal cancer may benefit from Her2 inhibitors. Therapy resistance, however, is well documented. Since autophagy, a lysosome-dependent catabolic process, is implicated in cancer resistance mechanisms, we tested whether autophagy modulation influences Her2 inhibitor sensitivity in EAC. Her2-positive OE19 EAC cells showed an induction in autophagic flux upon treatment with the small molecule Her2 inhibitor Lapatinib. Newly generated Lapatinib-resistant OE19 (OE19 LR) cells showed increased basal autophagic flux compared to parental OE19 (OE19 P) cells. Based on these results, we tested if combining Lapatinib with autophagy inhibitors might be beneficial. OE19 P showed significantly reduced cell viability upon double treatment, while OE19 LR were already sensitive to autophagy inhibition alone. Additionally, Her2 status and autophagy marker expression (LC3B and p62) were investigated in a treatment-naïve EAC patient cohort (n = 112) using immunohistochemistry. Here, no significant correlation between Her2 status and expression of LC3B and p62 was found. Our data show that resistance to Her2-directed therapy is associated with a higher basal autophagy level, which is not per se associated with Her2 status. Therefore, we propose that autophagy may contribute to acquired resistance to Her2-targeted therapy in EAC, and that combining Her2 and autophagy inhibition might be beneficial for EAC patients.

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“…Pembrolizumab and nivolumab are an anti-PD1 monoclonal antibody, and they facilitated the capacity of the immune system. A phase II study (KEYNOTE-059) demonstrated that application of pembrolizumab alone showed clinical efficacy in previously treated advanced GC[ 66 ]. Treatment of pembrolizumab showed a higher overall response rate (ORR) for patients with PD-L1 positive tumors, than in patients with PD-L1 negative tumors.…”

Section: Current Topics Of Biomarkers In Gcmentioning

confidence: 99%

Biomarkers of gastric cancer: Current topics and future perspective

Matsuoka

Yashiro

2018

WJG

363

266

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Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.

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Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma

Cited by 20 publications

References 122 publications

Targeted literature review of the global burden of gastric cancer

Targeted literature review of the global burden of gastric cancer

Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells

Biomarkers of gastric cancer: Current topics and future perspective

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