Evidence map›Paper›PMID 31715423›Full record

ReviewCancer treatment reviews2019

Molecular insight of regorafenib treatment for colorectal cancer.

Hiroyuki Arai, Francesca Battaglin, Jingyuan Wang, Jae Ho Lo, Shivani Soni, Wu Zhang, Heinz-Josef Lenz

Registry-linked trialOpen access · greenAbstract readReview
In one paragraph

Review in Cancer treatment reviews, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05557656 (A Real World Study of Regogfinib in the Treatment of Advanced Hepatocellular Carcinoma), which is not on this map. Cited by 102 papers.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05557656 unknown statusnot on this mapstarted 2023, after this paper: background citation

A Real World Study of Regogfinib in the Treatment of Advanced Hepatocellular Carcinoma

TypeobservationalSponsorZhongda HospitalRan2023 to 2023Enrolled800ConditionsHepatocellular CarcinomaArmsRegorafenib 40 MG
3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 200 citations in OpenAlex.

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  20. Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025
    Review

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Hiroyuki AraiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States.
Francesca BattaglinDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States. Electronic address: fbattagl@usc.edu.
Jingyuan WangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States. Electronic address: 1811110576@bjmu.edu.cn.
Jae Ho LoDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States. Electronic address: jaeholo@usc.edu.
Shivani SoniDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States.
Wu ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States. Electronic address: Wu.Zhang@med.usc.edu.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlate Avenue, Los Angeles, CA 90033, United States. Electronic address: lenz@usc.edu.
University of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

Regorafenib is a multi-targeting kinase inhibitor approved for the treatment of metastatic colorectal cancer patients in refractory to standard chemotherapy. Similarly to sorafenib, this agent was originally developed as a RAF1 inhibitor. However, the kinase inhibitory profile is distinct from sorafenib. A broad-spectrum of kinase inhibition induces wide-range drug sensitivity, irrespective of mutation status of major oncogenes. This agent's main therapeutic effects are anti-angiogenesis and the remodeling of tumor microenvironment through several mechanisms of action. The dual blockade of VEGF receptors and TIE2 can lead to both additive anti-angiogenesis effects and the suggestive unique regulation of vessel stability. Additionally, it inhibits molecular escape pathways to VEGF inhibition (e.g., FGF, PIGF, and PDGF signaling), enabling its continuous antiangiogenic effect even in tumors resistant to VEGF inhibitors. Furthermore, regorafenib has the important effect of enhancing anti-tumor immunity via macrophage modulation. Based on this concept, clinical trials have been recently launched for the development of a combination strategy with immune checkpoint inhibitors. Contrary to regorafenib induced clinical benefits and advances in the novel strategy, currently no predictive biomarkers have been identified. In the present review, we revisit and summarize regorafenib's unique mechanisms of action. The review could highlight molecular insights and provide some perspective for the search of predictive biomarkers used in metastatic colorectal cancer patients treated with regorafenib.

Indexed as

Angiogenesis InhibitorsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorColorectal NeoplasmsHumansMacrophagesMutationPhenylurea CompoundsProto-Oncogene Proteins B-rafPyridinesras ProteinsReceptors, Vascular Endothelial Growth FactorReceptor, TIE-2Angiogenesis InhibitorsAntineoplastic AgentsBiomarkers, TumorBRAF protein, humanPhenylurea CompoundsProto-Oncogene Proteins B-rafPyridinesras ProteinsReceptors, Vascular Endothelial Growth FactorReceptor, TIE-2regorafenibTEK protein, humanAnti-angiogenesisBiomarkerColorectal cancerImmunotherapyRegorafenibTumor microenvironment

Identifiers

PMID31715423
PMCPMC7491975
OpenAlexW2982376008

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.