Systemic therapy for advanced gastrointestinal stromal tumors: Beyond imatinib

Kim, Edward; Zalupski, Mark M.

doi:10.1002/jso.21872

Cited by 22 publications

(9 citation statements)

References 43 publications

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“…Masitinib is an oral tyrosine kinase inhibitor that acts on KIT, PDGFR (A + B), and LYN [66, 67]. It has been found to be superior to IM in antitumor activity and selectivity against those tumors lacking a kinase mutation or those with a KIT exon 11 mutation [68].…”

Section: Kit and Pdgfra Inhibitorsmentioning

confidence: 99%

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Alturkmani

Pessetto

Godwin

2015

Expert Opinion on Investigational Drugs

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Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival.

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Section: Kit and Pdgfra Inhibitorsmentioning

confidence: 99%

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Alturkmani

Pessetto

Godwin

2015

Expert Opinion on Investigational Drugs

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“…Although Gleevec/STI-571, an inhibitor of Tyr kinases (ABL/c-KIT/PDGFR), was successfully developed around the turn of this century as the very first "signal therapeutic" (antioncogenic signal blocker) and serves as a sort of "miracle" drug for a few rare cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumor [161,162], these cancers altogether represent less than 0.1 % of all human cancers, and Gleevec is basically useless for the remaining more than 99% of human cancers whose growth is independent of these specific Tyr kinases.…”

Section: Discussionmentioning

confidence: 99%

Oncogenicity of PAKs and Their Substrates

Miyata²

2013

Paks, Rac/Cdc42 (P21)-Activated Kinases

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“…Marker for late stage gastric cancer [137] Other candidates CC-chemokines (CCL2, 3, 5, 21, 25)/CXC-chemokines (1,7,8,12,14)/CCR6 [139] Liver CXCR4 Metastasis, upregulation in PVTT [142][143] …”

Section: Cxcl5mentioning

confidence: 99%

“…Amongst these, which include growth factors and their receptors [7][8][9] , signaling pathway components [10,11] , transcription factors [12,13] , matrix remodeling enzymes [14,15] and cytokines [16][17][18] , a milestone finding by Müller et al [19] made chemokines one of the most intensively studied molecular targets to understand the mechanisms of organspecific metastasis. The chemotactic cytokines or chemokines contribute to the tumor microenvironment by establishing a chemokine gradient, which is important for the process of chemoattraction and subsequent cell motility and infiltration for metastasis [20,21] .…”

Section: Introductionmentioning

confidence: 99%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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Systemic therapy for advanced gastrointestinal stromal tumors: Beyond imatinib

Cited by 22 publications

References 43 publications

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Oncogenicity of PAKs and Their Substrates

Chemokines, chemokine receptors and the gastrointestinal system

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