Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.

/pdf/advances-in-targeted-therapy-for-esophageal-cancer-3ooknk7eaz.pdf

Advances in targeted therapy for esophageal cancer.

The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody‒drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future. 

/pdf/small-molecule-inhibitors-immune-checkpoint-inhibitors-and-cqpiwni3.pdf

Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Introduction: Ramucirumab (IMC-1121B) is a fully humanized IgG1 monoclonal antibody, targeting the extracellular domain of VEGF receptor 2 (VEGFR2). Numerous Phase I – II trials in various malignancies have shown promising clinical antitumor efficacy and tolerability. Most recently, the large Phase III REGARD trial evaluated ramucirumab in patients with refractory metastatic gastric cancer. Patients receiving ramucirumab experienced a median overall survival of 5.2 months compared to 3.8 months on placebo. Areas covered: The purpose of this article is to review the preclinical motivation for VEGFR2-targeted therapies and survey recent data from clinical trials involving ramucirumab, as well as highlight ongoing studies. Expert opinion: Rational multi-target approaches to angiogenesis are needed to overcome resistance mechanisms. Predictive angiogenic biomarkers are also needed to optimize patient selection for novel anti-angiogenic agents.

Targeted inhibition of VEGF receptor 2: an update on ramucirumab

Gastric cancer is the fourth most common cancer globally and represents the second most common cause of cancer mortality. Early detection, aggressive surgical resection and postoperative adjuvant therapy has led to survival improvement for early stage gastric cancer, particularly in Asian countries. Unfortunately, advanced gastric cancer continues to pose a formidable challenge with few gains being reported recently. Trastuzumab was the first targeted agent to be approved for the treatment of advanced gastric cancer in 2010. The failure of the AVAGAST trial was a setback for anti-angiogenic therapy for this disease. Ramucirumab is a monoclonal antibody that binds to VEGF-R2 and prevents its activation. The recent REGARD trial was a randomized phase III trial of ramucirumab vs. placebo for patients with advanced, pre-treated gastric cancer that met its primary endpoint of increased overall survival. The toxicity of ramucirumab was modest in this setting, with an increased risk of grade 3 or higher hypertension (8% vs. 3%, with ramucirumab and placebo, respectively). The subsequent RAINBOW trial of paclitaxel plus ramucirumab vs. paclitaxel plus placebo for advanced pretreated gastric cancer confirmed the survival advantage of this antiangiogenic agent in gastric cancer. Ramucirumab is the first FDA approved therapy for advanced gastric cancer after prior chemotherapy.

https://clincancerres.aacrjournals.org/content/clincanres/20/23/5875.full.pdf

Ramucirumab: Successfully Targeting Angiogenesis in Gastric Cancer

Following Milstein’s discovery, the monoclonal antibodies (mAbs) became a basic tool for biomedical science. In cancer field, since the first mAb was approved by the FDA a great improvement took place making of them a therapeutic option for many cancer types in the current clinical practice. Today, mAbs are being developed to target different molecules with different mechanisms of action and its target potential is unlimited. However, this huge and fast growing new field needs to be organized to better understand the treatment options we have to confront different cancer diseases. Current cancer targeted immunotherapies aim to achieve different goals like the regulation of osteoclast function, the delivery of cytotoxic drugs into tumor cells and the blockade of oncogenic pathways, neo-angiogenesis and immune checkpoints. Here, we reviewed the most relevant therapeutic mAbs for solid tumors available in current clinical practice.

/pdf/state-of-the-art-in-anti-cancer-mabs-3y2pvgiuay.pdf

State of the art in anti-cancer mAbs.

3984 Neutralizing antibodies to the RON-receptor tyrosine kinase were generated and compared for their effects on multiple tumor cell lines and xenograft models. RON, known as the macrophage-stimulating protein receptor (MSP-R), belongs to the c-Met family of receptor tyrosine kinases. RON is normally expressed in multiple epithelial cell types and evidence suggests it has a role in cancer. It is highly expressed in several epithelial tumors and cell lines of the colon, lung, breast, stomach, ovary, pancreas, bladder, liver, and kidney. In addition, RON activation leads to activation of signaling pathways involved in tumorigenesis. An initial antibody termed 41A10, henceforth designated RON-1, was derived from a phage system and showed inhibition of RON-dependent cell-signaling and tumor growth. Here we report the identification of novel anti-RON antibodies generated from a transgenic mouse system. Antibodies RON-6 and RON-8 have an affinity for the RON-receptor that is 100 fold greater than RON-1. Specifically, RON-6 and RON-8 bind RON with a K D of 4.1 x 10 -11 and 3.2 x 10 -11 M whereas RON-1 binds RON with a K D of 7.7 x 10 -9 M. Phosphorylation of MAPK is a necessary step in cell growth and this pathway is activated by the RON receptor. RON-6 proved to be less active than RON-8 in cell-based assays at inhibiting RON and MAPK phosphorylation in transfected and tumor cell lines. The in vivo anti-tumor activity of RON-1, RON-6 and 8 was compared in colon (HT-29) and lung (NCI-H292) xenograft tumor models in nude mice. All antibodies showed evidence of efficacy but RON-8 consistently outperformed RON-1 and RON-6 by significantly inhibiting the growth of colon and lung xenograft tumors at 60 mg/kg administered twice a week. RON-8 also proved effective at inhibiting the growth of a pancreatic tumor xenograft (BXPC3). These data suggest RON-8 may be useful for the treatment of tumors that express RON.

In vitro characterization and in vivo anti-tumor activity of human monoclonal antibodies to the RON-receptor tyrosine kinase

The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Pinki Singh

Author Tools

Chat about Author

Papers

In vitro characterization and in vivo anti-tumor activity of human monoclonal antibodies to the RON-receptor tyrosine kinase

The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies