Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma

Young, Kate; Smyth, Elizabeth; Chau, Ian

doi:10.1177/1756283x15592586

Cited by 26 publications

(12 citation statements)

References 27 publications

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“…Gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide (5,6). Presently, there are only three FDA-approved drugs that target gastric cancer: Trastuzumab (7,8), Ramucirumab (9)(10)(11), and pembrolizumab (12). These drugs have great efficacy in some cancer types such as breast cancer or colon cancer but are much less effective in treating gastric cancer, especially advanced gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

PIWIL1 promotes gastric cancer via a piRNA-independent mechanism

Shi

Yang

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Targeted cancer therapy aims to achieve specific elimination of cancerous but not normal cells. Recently, PIWI proteins, a subfamily of the PAZ-PIWI domain (PPD) protein family, have emerged as promising candidates for targeted cancer therapy. PPD proteins are essential for small noncoding RNA pathways. The Argonaute subfamily partners with microRNA and small interfering RNA, whereas the PIWI subfamily partners with PIWI-interacting RNA (piRNA). Both PIWI proteins and piRNA are mostly expressed in the germline and best known for their function in transposon silencing, with no detectable function in mammalian somatic tissues. However, PIWI proteins become aberrantly expressed in multiple types of somatic cancers, thus gaining interest in targeted therapy. Despite this, little is known about the regulatory mechanism of PIWI proteins in cancer. Here we report that one of the four PIWI proteins in humans, PIWIL1, is highly expressed in gastric cancer tissues and cell lines. Knocking out the PIWIL1 gene (PIWIL1-KO) drastically reduces gastric cancer cell proliferation, migration, metastasis, and tumorigenesis. RNA deep sequencing of gastric cancer cell line SNU-1 reveals that KO significantly changes the transcriptome, causing the up-regulation of most of its associated transcripts. Surprisingly, few bona fide piRNAs exist in gastric cancer cells. Furthermore, abolishing the piRNA-binding activity of PIWIL1 does not affect its oncogenic function. Thus, PIWIL1 function in gastric cancer cells is independent of piRNA. This piRNA-independent regulation involves interaction with the UPF1-mediated nonsense-mediated mRNA decay (NMD) mechanism. Altogether, our findings reveal a piRNA-independent function of PIWIL1 in promoting gastric cancer.

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Section: Introductionmentioning

confidence: 99%

PIWIL1 promotes gastric cancer via a piRNA-independent mechanism

Shi

Yang

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…[17,19] A few targeted agents like trastuzumab in HER-2 positive adenocarcinoma, ramucirumab and bevacizumab in junctional adenocarcinoma, nivolumab & pembrolizumab in PDL1 (programmed death-ligand 1) overexpressed tumor are well approved therapy with proved benefit. [20][21][22][23][24] The role of some other targeted therapy like cetuximab, gefitinib and erlotinib, nimotozumab, panitimumab, sunitinib, entrectinib, larotrectinib in advanced, metastatic and recurrent esophageal cancer is evaluated in different studies but yet to established conclusively. [15,[25][26][27] Patient with very advanced disease and morbid general condition sometimes only require palliative treatment.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Review of Esophageal Carcinoma: 3-Year Experience from a Tertiary Care Teaching Institute

Paul

Kumar

Dhull

2021

Int J Health Sci Res

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Introduction: Esophageal carcinoma, one of the common malignancies, generally presented in advanced stage makes these neoplasms less curable and highly lethal. Having such poor prognosis, it is significant to understand various patient and tumor facts related to treatment outcome of esophageal cancer, which varies regions wise. The present retrospective study also seeks to focus on current description of patterns and trends of tumors in esophageal cancer patients attended in a tertiary care hospital in a northern state of India and their treatment outcome. Materials and Methods: Records of esophageal carcinoma patients over a period of 3-years were reviewed retrospectively. These records were analysed for incidence, demographic pattern, different treatment modalities and their response evaluation. Results: A total 439-patients of esophageal carcinoma were identified. The median age at presentation was 47-years and males slightly outnumbered females. Among all the tumors, lower thoracic esophagus involvement was most predominant and most common presentation was dysphagia. Squamous cell carcinoma constituted the predominant histopathological type. Majority of patients presented in advanced stage and treated with combined modalities approach of radiation therapy, chemotherapy and surgery. Overall average survival was 13-months. Clinically, the response at last follow-up was CR in 19%, PR and PD in 33% each. Conclusion: Despite its high prevalence in north India and poor survival rate, less initiative has been taken to increase awareness in preventing these cancers. Understandings of socio-demographic patterns and tumor characteristics may improve treatment outcome in these patients and improve quality of life. Further studies are needed in different regions of India, to get more treatment options which may convert the current scenario of palliative intent in to radical one in patients of esophageal carcinoma. Key words: Esophageal carcinoma, retrospective study, socio-demographic profile, dysphagia, squamous cell carcinoma.

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“…First published results demonstrated promising results for this biological drug, indicating that combination of ramucirumab with paclitaxel or platinum-containing or fluoropyrimidine-containing chemotherapy increases overall survival, progression-free survival as well as quality of life when compared to chemotherapy-only arm [48][49][50]. In 2014, FDA approved the addition of ramucirumab to paclitaxel as the treatment for patients with advanced GC or GEJ adenocarcinoma as well as its use as monotherapy for patients who did not respond to the first-line therapy with platinum-or fluoropyrimidine-containing chemotherapy [51].…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Clinical Implications of Molecular Heterogeneity of Gastric Cancer

Hudler¹,

Komel²

2017

Gastric Cancer

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Gastric cancer incidence has been steadily declining in countries with low frequencies of gastric carcinoma since early 1930s. In areas with higher incidences, the decline has been less obvious and slower. Nevertheless, gastric adenocarcinoma remains one of the most common causes of cancer-related death worldwide. The poor outcome has been attributed to late detection of the condition, particularly in Americas and Europe, aggressive pathogenesis and lack of symptoms during early stages of the tumor development. In addition, sporadic stomach cancer mostly affects elderly individuals. In the majority of countries with low incidence, the average age at the disease presentation is above 65. Therefore, gastric adenocarcinoma, among other diseases associated with old age, raises health concerns in countries with changing demographic age profiles that show a trend of an increase in the proportion of the population aged over 60. The low 5-year survival rate of patients underscores the critical need for the development of more accurate diagnostic tools and safe targeted chemotherapeutics. However, the heterogeneity of molecular changes represents one of the most pressing issues in the current research of gastric cancer, impeding the translation of genetic aberrations into novel applications for medical practice.

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Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma

Cited by 26 publications

References 27 publications

PIWIL1 promotes gastric cancer via a piRNA-independent mechanism

PIWIL1 promotes gastric cancer via a piRNA-independent mechanism

Retrospective Review of Esophageal Carcinoma: 3-Year Experience from a Tertiary Care Teaching Institute

Clinical Implications of Molecular Heterogeneity of Gastric Cancer

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