Apatinib for the treatment of gastric cancer

Geng, Ruixuan; Li, Jin

doi:10.1517/14656566.2015.981526

Cited by 84 publications

(67 citation statements)

References 39 publications

(10 reference statements)

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“…In recent years, although a number of newer chemotherapeutic agents and regimens significantly improved the median survival time, the overall benefits are still limited [6][7][8]. Multidrug resistance (MDR), referring to the development of resistance to multiple chemotherapeutic agents after exposure to a single agent, or even on initial exposure, is the major cause of failure in chemotherapy and the high mortality [9].…”

Section: Introductionmentioning

confidence: 99%

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HNRNPC as a candidate biomarker for chemoresistance in gastric cancer

et al. 2015

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Chemoresistance is a major cause of treatment failure and high mortality in advanced gastric cancer (AGC). Currently, the mechanism of chemoresistance remains unclear, and there is no biomarker to accurately predict the efficacy of chemotherapy. In the present study, we established human gastric cancer (GC) cell lines resistant to 5-fluorouracil (5FU), paclitaxel (TA), or cisplatin (DDP) by gradient drug treatment and generated a novel monoclonal antibody 5B2 targeting heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) overexpressed in chemoresistant GC cells. Overexpressing HNRNPC in GC cells promoted chemoresistance, and knockdown of HNRNPC by small interfering RNA (siRNA) reversed chemoresistance. By utilizing available datasets, we demonstrated that high level of HNRNPC transcript indicated poor overall survival (OS) and free of progression (FP). HNRNPC expression was negatively correlated with OS of GC patients treated with 5FU-based drugs and with time to progression (TTP) of GC patients treated with CF regimen. These data suggest the potential usefulness of HNRNPC as a prognostic and therapeutic marker of GC.

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Section: Introductionmentioning

confidence: 99%

“…Several cancer biomarkers had been screened by immunizing mice with cultured cancer cells to generate mAbs [10][11][12][13]. Antibody-based targeted cancer therapy, such as cetuximab, trastuzumab, bevacizumab, and other antibodybased inhibitors, has shown increasing clinical efficacy in the treatment of a number of cancers [7,8,14].…”

Section: Introductionmentioning

confidence: 99%

HNRNPC as a candidate biomarker for chemoresistance in gastric cancer

et al. 2015

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“…Apatinib is an anti-VEGF-2 small molecule TKI evaluated in China [124]. Phase II and III studies have shown that apatinib was the irst discovered anti-VEGF-2 molecule TKI with beneits for Asian patients with advanced gastric cancer [125], representing a signiicant progress for third-line treatment, although it prolonged OS by less than 2 months.…”

Section: Tkis Of Vegfmentioning

confidence: 99%

Molecular Prognostic Factors in Gastric Cancer

Lazăr¹,

Tăban²,

Cornianu³

et al. 2017

Gastric Cancer

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Gastric cancer represents a major health problem worldwide. Literature data have demonstrated that gastric tumors present a high molecular heterogeneity, responsible for the process of carcinogenesis and dissemination. By revealing the molecular subtype of the tumor, it is possible to assess its behavior, the outcome of the patient, and the treatment approach, according to its genetic and epigenetic proile. This chapter aims to highlight some of the many diferent genetic mutations, epigenetic alterations, as well as aberrant signaling pathways involved in the pathogenesis of stomach cancers, each of these molecular abnormalities acting in a speciic stage of the disease. Moreover, the manuscript describes the novel therapeutic agents that target some of these aberrant molecular signaling pathways. Unfortunately, only a few agents are currently part of the standard treatment of gastric cancer, while most of the others remain to prove their therapeutic eicacy in the seting of clinical trials. By discovering the diferent molecular subtypes of gastric cancer, as well as numerous classes of targeted molecular agents, in the future, we would be able to perform an individualized treatment, associated with maximum eiciency and less costs.Keywords: gastric cancer, molecular classiication, gene expressions-based prognostic scoring system, molecular biomarkers, molecular targeted treatment IntroductionDespite a decline in the incidence in past decades, gastric cancer remains a major health problem globally [1,2], being the ifth most common type of cancer worldwide, with almost one million new cases estimated to have occurred in 2012, according to Globocan [3]. Furthermore, stomach cancer represents the third leading cause of cancer death in both sexes worldwide (723,000 deaths) [3].© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.According to the World Health Organization classiication, the vast majority of gastric cancers are adenocarcinomas, divided into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas (including signet-ring cell carcinoma and other variants) [4]. Although it was proposed a long time ago (1965), the Lauren classiication is still widely used in clinical practice and subdivides gastric carcinomas into intestinal and difuse types, associated with diferent pathogenesis, ways of spreading, and outcome [5]. Unfortunately, these two classiication systems have litle clinical impact, making the development of classiiers that can deine prognosis and guide patient's treatment as an urgent need.Literature data have demonstrated that the development of gastric cancer is associated in the majority of cases with infectious agents such as the Gram-negative spiral bacterium Helicobacter pylori (most often) [6] and Epstein-Barr virus (EBV) (about 9% o...

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“…[5] Phase II and III clinical trials suggest apatinib can improve OS and progression-free survival (PFS) in advanced gastric cancer patients who have experienced treatment failure on 2 or more prior chemotherapy regimens. Apatinib was approved and launched in the People's Republic of China in 2014 as a second-line treatment for gastric cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Concurrent apatinib and local radiation therapy for advanced gastric cancer

et al. 2017

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Rationale:Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer.Patient concerns and Diagnoses:we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy.Interventions and Outcomes:The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection.Lessons:Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer.

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Apatinib for the treatment of gastric cancer

Abstract: Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.

Cited by 84 publications

References 39 publications

HNRNPC as a candidate biomarker for chemoresistance in gastric cancer

HNRNPC as a candidate biomarker for chemoresistance in gastric cancer

Molecular Prognostic Factors in Gastric Cancer

Concurrent apatinib and local radiation therapy for advanced gastric cancer

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