Overview of Gastric Cancer Treatment and Recent Developments – An Updated Review (original) (raw)
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Recommendations on current approach to gastric cancer
Clinical and Translational Oncology, 2009
The management of gastric cancer has been updated by the Grupo Español de Tratamiento de Tumores Digestivos (TTD). A multidisciplinary approach is essential in these patients including a precise diagnosis and staging and correct nutritional evaluation. For resectable disease, surgical resection remains the treatment mainstay and both perioperatory chemotherapy and postoperatory chemoradiotherapy are considered standard complementary treatments. In advanced disease chemotherapy should always be considered. There are different reference schemes (TCF, XC, ECF, EXC) and the therapeutic option has to be individualised. Recently a phase III trial has shown a significant improvement in overall survival when trastuzumab is added to cisplatin-capecitabine or cisplatin-5-fl uorouracil in patients with HER2+ advanced gastric cancer. Currently, there are several ongoing clinical trials evaluating the role of other new drugs against cellular targets. It would be desirable to incorporate biomarker studies in these trials in order to identify the best treatment for each patient.
Targeted therapy for gastric cancer--current status
Journal of Oncology Pharmacy Practice, 2012
According to the 2012 statistics of the International Agency for Research on Cancer (IARC), gastric cancer is the fifth most common malignancy, and the third leading cause of cancer-related deaths worldwide. Conventional chemotherapy and radiation have shown limited efficacy for advanced gastric cancer, showing an overall survival (OS) rate of ~10 months. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is the first approved molecularly targeted agent for HER2-overexpressing gastric cancer, which was found to prolong the OS and the progression-free survival (PFS) of patients. However, HER2 overexpression is present only in a minority of patients with gastric cancer. Hence, other targeted agents are urgently needed. Ramucirumab, a novel human IgG1 monoclonal antibody that selectively targets the extracellular domain of VEGF receptor 2 (VEGFR2), is regarded as a new standard secondline treatment for patients with advanced gastric cancer. The combination of two or more targeted agents directed against two different molecular targets may improve the survival of patients with advanced gastric cancer. Although great efforts have been made, the effect of targeted therapy for gastric cancer is limited. One key reason is that participants in clinical trials for new targeted agents were not selected by detection of the targeted molecule. Here, we review clinical trials related to molecular targets such as anti-epidermal growth factor receptor signaling including anti-HER2 and anti-EGFR1, anti-VEGF signaling, anti-mammalian target of rapamycin (mTOR), tyrosine kinase inhibitors (TKIs) and anti-MET. Contents 1. Introduction 2. Anti-EGFR signaling 3. Anti-VEGF signaling 4. Tyrosine kinase inhibitors 5. mTOR inhibitors 6. Anti-MET pathway 7. Other target agents and future directions 8. Conclusions
Gastric cancer is one of the leading causes of cancer-related death worldwide. Many patients have inoperable disease at diagnosis or have recurrent disease after resection with curative intent. Gastric cancer is separated anatomically into true gastric adenocarcinomas and gastro-oesophageal-junction adenocarcinomas, and histologically into diff use and intestinal types. Gastric cancer should be treated by teams of experts from diff erent disciplines. Surgery is the only curative treatment. For locally advanced disease, adjuvant or neoadjuvant therapy is usually implemented in combination with surgery. In metastatic disease, outcomes are poor, with median survival being around 1 year. Targeted therapies, such as trastuzumab, an antibody against HER2 (also known as ERBB2), and the VEGFR-2 antibody ramucirumab, have been introduced. In this Seminar, we present an update of the causes, classifi cation, diagnosis, and treatment of gastric cancer.
Gastric cancer and the epoch of immunotherapy approaches
World journal of gastroenterology : WJG, 2015
The incidence of gastric cancer (GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancer-related deaths with a case fatality GC ratio higher than other common malignancies. Surgical resection is the primary curative treatment for GC though the overall 5-year survival rate remains poor (approximately 20%-25%). To improve the outcome of resectable gastric cancer, different treatment strategies have been evaluated such as adjuvant or perioperative chemotherapy. In resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit. Moreover, in metastatic patients, chemotherapy is the mainstay of palliative therapy with a median overall survival of 8-10 mo and objective response rates of merely 20%-40%. Therefore, the potential for making key beneficial progress is to investigate the GC molecular biology to realize innovative therapeutic strategies, such as speci...
Recent Advances in Systemic Treatments for HER-2 Positive Advanced Gastric Cancer
OncoTargets and Therapy, 2021
Gastric cancer (GC) is the fifth most common cancer worldwide. Despite recent improvements in treatment quality and options, advanced gastric cancer remains one of the hardest to cure cancers, with a median overall survival (OS) of 10-12 months and a 5-year OS of approximately 5-20%. There is an unmet need for further efforts to palliate diseaserelated symptoms, improve quality of life, increase tumor response rate, and prolong progression free and overall survival while balancing the toxicities of therapy. The most common type of GC is adenocarcinoma, which demonstrates morphological, biological, and clinical heterogeneity. A plethora of genomic alterations and the activation of numerous molecular pathways including human epidermal growth receptor 2 (HER2), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor-2 (FGFR2), mesenchymal epidermal transforming factor receptor (MET), and the phosphatidylinositol 3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) are responsible for the complex heterogeneity of GC. Efforts to validate the therapeutic effects of inhibiting some of these aberrantly expressed pathways have failed to lead to a clinically meaningful outcome apart from the overexpression/amplification of the HER2 gene, inhibition of which has had a significant impact on clinical practice. The only available biomarkers to guide the effective treatment of patients with advanced GC are HER2 overexpression, MSI/PD-L1 status, and FGFR alterations. Various anti-HER2 agents have been evaluated after the success of the ToGA trial, but none led to a significant enough clinical improvement to be considered a viable alternative for HER2-targeted therapy in advanced GC until the global Keynote-811 trial, which added pembrolizumab to trastuzumab in combination with chemotherapy. This combination demonstrated a survival advantage for the first time in the 11 years since ToGA. Trastuzumab deruxtecan (T-DXd) was also found to be effective in patients who had already received >2 previous lines of treatment. Despite these promising avenues, the optimal management of HER-2 positive GC still requires further development.
HER2 therapies and gastric cancer: a step forward
World Journal of Gastroenterology, 2013
Gastric cancer usually is diagnosed in advanced stages and thus current medical practice affords limited therapeutic options. However, recent studies established the role of human epidermal growth factor receptor 2 (HER2) in clinical management. Trastuzumab, an anti-HER2 monoclonal antibody, acquired a main role in advanced gastric cancer harboring HER2 overexpression and/or amplification improving survival to 17.1 mo according to trastuzumab for gastric cancer phase Ⅲ trial results. Also, new promising drugs, such as c-Met inhibitors, are in development and assessment for this setting. Certainly, novel drugs will emerge in the next feel years for help oncologists improve clinical management of advanced gastric cancer providing higher survival and quality of life. In this mini-review we will discuss some issues in this regard and provide an actual overview of this setting.
Seom guidelines for the treatment of gastric cancer 2015
Clinical and Translational Oncology, 2015
Gastric cancer is the fourth cause of death by cancer in Spain and a significant medical problem. Molecular biology results evidence that gastroesophageal junction tumors and gastric cancer should be considered as two independent entities with a different prognosis and treatment approach. Endoscopic resection in very early tumors is feasible. Neoadjuvant and adjuvant therapy in locally advanced resectable tumor increase overall survival and should be considered standard treatments. In stage IV tumors, platinum-fluoropyrimidine-based schedule, with trastuzumab in HER2-overexpressed tumors, is the firstline treatment. Different therapies in second line have demonstrated in randomized studies their clear benefit in survival improvement.
New therapeutic targets in the management of advanced gastric cancer
Academia Oncology, 2024
Treatment of advanced gastric cancer remains challenging due to its late diagnosis and aggressive nature. HER2 inhibitors like trastuzumab deruxtecan (T-DXd) show significant efficacy in HER2-positive gastric cancer. Zolbetuximab targets CLDN18.2, inducing immune-mediated cancer cell destruction. Bemarituzumab targets FGFR2b, showing promising results in clinical trials. Immune checkpoint inhibitors such as pembrolizumab and nivolumab enhance the immune response against cancer and improves survival. This review highlights the transformative potential of emerging therapeutic targets in the fight against advanced gastric cancer, emphasizing the need for ongoing innovation and clinical research.
Targeted Therapies for Gastric Cancer
Drugs, 2011
Gastric cancer represents one of the most common cancers internationally. Unfortunately the majority of patients still present at an advanced stage, and despite advances in diagnostic and treatment strategies, outcomes still remain poor with high mortality rates despite a decline in incidence. Whilst the utility of classical chemotherapy agents has been explored thoroughly (and continues to be investigated, alone or in various combinations), advances have been slow and the efficacy of these agents has reached a plateau. As such, the focus of recent study has shifted toward developing a greater understanding of the molecular biology of carcinogenesis and the cancer cell phenotype, and, in turn, the development of rationally designed drugs that target molecular aberrancies in signal transduction pathways specific to gastric cancer. These targets include circulating growth and angiogenic factors, cell surface receptors, and other molecules that comprise downstream intracellular signalling pathways, including receptor tyrosine kinases. Therapeutic advances in this area significantly lag behind other solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted therapies in gastric cancer, including rationale and mechanism of action, current and emerging data, as single-agent therapy or in combination regimens. A recently published randomized phase III trial supporting the use of trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2)/neu monoclonal antibody, in a selected population of patients is discussed. Therapies that have been evaluated in phase II trials are also reviewed, as well as promising new therapies currently being investigated in preclinical or phase I studies. There is optimism that targeted therapies, whether as single-agent therapy or in combination with traditional therapies, including chemotherapy, radiotherapy and surgery, may yet have an impact on improvement of the overall prognosis of gastric cancer.
International Journal of Research in Pharmaceutical Sciences
Gastric Cancer (GC) is one of the serious diseases prevailing globally. GC has immense global life-threatening health issues by taking 4th place among all the widespread cancers and 2nd foremost reason for fatality around the globe. Numerous patients have inoperable disease at diagnosis or have recurrent disease after resection with curative intent. In the present review, we have put forward all the possible advanced treatments for GC, which includes the application of Nanotechnology, Monoclonal antibodies, and Robotic surgery. Nanoparticle offers a potentially improved treatment of multidrug-resistant cancers. GC is uniquely positioned as an area of research for targeted and nanoparticle therapies. This review briefs about design and considerations to develop targeted nanoparticle-based approaches for overcoming physiological hurdles in GC treatment. Based on current knowledge, molecular and cellular mechanisms, a number of novel biologic approaches such as monoclonal antibodies ha...