Targeted Therapy in Gastrointestinal Stromal Tumors

Rutkowski, Piotr; Przybył, Joanna; Woźniak, Agnieszka; Badalamenti, Giuseppe

doi:10.1007/978-1-4939-2047-1_14

Cited by 2 publications

(2 citation statements)

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“…They are characterized by a predominant location in the stomach, multifocality, propensity for lymphatic spread and often indolent clinical behaviour even in metastatic disease [21,22]. SDH-deficient GISTs usually develop early in childhood and in adolescents/young adults [2]. However, patients in their forties or fifties may also emerge with an initial diagnosis of SDH-deficient GIST.…”

Section: Clinical and Molecular Features Of Sdh-deficient Gistsmentioning

confidence: 99%

“…Gastrointestinal stromal tumours (GIST) comprise a heterogeneous group of the most common mesenchymal neoplasms of the gastrointestinal tract. Most GIST are related to activating, somatic, mutually exclusive mutations of two genes -KIT and PDGFRA (platelet-derived factor receptor-alpha), which are early oncogenic events during GIST development [1][2][3]. Advances in the understanding of molecular events underlying GIST tumorigenesis have led to an awareness of the essential role of KIT and PDGFRA oncoproteins as diagnostic and thera-peutic targets, and to the paradigm for molecularly targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

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SDH-deficient gastrointestinal stromal tumours

Rutkowski

Seliga

Dębiec‐Rychter

2022

Nowotwory. Journal of Oncology

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Gastrointestinal stromal tumours (GIST) comprise a heterogeneous group of the most common mesenchymal neoplasms of the gastrointestinal tract. The majority of GIST are induced by activating, mutually exclusive mutations of two genes -KIT and PDGFRA (platelet-derived growth factor receptor-alpha). However, approximately 10-15% of GISTs lack oncogenic KIT or PDGFRA mutations and these tumours are often called "wild type" (WT) GISTs. The SDH-deficient GISTs form a distinctive subset of tumours accounting for 20-40% of KIT/PDGFRA WT GIST, which results from the loss of function mutations in the genes encoding the SDH enzyme complex. The true frequency of SDH-deficient GISTs was reported to be approximately 7.4 to 7.7%. These tumours usually occur in the stomach (most commonly in the antrum) and have a spectrum of behaviour from indolent to progressive. In most cases the molecular mechanism behind the SDH-deficient GISTs is connected to germline mutations. SDHA germline mutations occur in approximately 30% of the SDH-deficient GIST, those in SDHB, SDHC, and SDHD appear in 20-30% of patients. The SDH-mutated GISTs do not respond well to the commonly used targeted therapy, with no objective tumour response to imatinib. Taking into account the biological features of SDH-deficient GIST, new therapies of potential interest comprise PI3K/AKT/mTOR inhibitors, heat-shock protein inhibitors, HIF1-α targeting agents, epigenetic modifiers and demethylating agents. However, further research is necessary in these fields.

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Section: Clinical and Molecular Features Of Sdh-deficient Gistsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%