Targeting Src in mucinous ovarian carcinoma

Matsuo, Keiichi; Nishimura, Masato; Bottsford-Miller, Justin; Stone, Richard; Zand, Behrouz; Shahzad, Mian M.K.; Schmeler, Katheleen M.; Wong, Kien Yee Michael; Frumovitz, Michael; Sood, Anil K.

doi:10.1016/j.ygyno.2011.12.012

Cited by 2 publications

(3 citation statements)

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“…Dasatinib is an SRC inhibitor and is used as a second‐line kinase inhibitor against chronic myelogenous leukemia. Preclinical and clinical studies have been conducted for lung cancer, 46 urothelial cancer, 47 and ovarian cancer 48 . A few researchers have considered SRC as a target for gastric cancer therapy 41 .…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical and clinical studies have been conducted for lung cancer, 46 urothelial cancer, 47 and ovarian cancer. 48 A few researchers have considered SRC as a target for gastric cancer therapy. 41 As our data showed, SRC amplification is more prevalent in node-positive and more advanced cases; thus, SRC amplification is likely to be an important clinical determinant of the outcomes of gastric cancer patients.…”

Section: Discussionmentioning

confidence: 99%

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Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization

Kiyose

Nagura

Hong

et al. 2012

Pathology International

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To test the feasibility of using bacterial artificial chromosomes (BAC) containing kinases for pathological diagnosis using fluorescence in situ hybridization (FISH), 10 BAC probes containing a gene amplified in 5% or more of a pilot cohort were selected from a previous survey using arbitrarily selected BAC clones harboring 100 kinases. In this report, we describe the prevalence and association with the clinicopathological profile of these selected 10 BAC probes in 365 gastric cancer tissues. FISH analyses using these 10 BAC probes containing loci encoding EGFR, ERBB2(HER2), EPHB3, PIK3CA, MET, PTK7, ACK1, STK15, SRC, and HCK showed detectable amplifications in paraffin-embedded tissue in 2.83% to 13.6% of the gastric cancer tissues. Considerable numbers of the cases showed the co-amplification of two or more of the probes that were tested. BAC probes located within a genome neighborhood, such as PIK3CA, EPHB3, and ACK1 at 3q26-29 or HCK, SRC, and STK15 at 20q11-13.1, were often co-amplified in the same cases, but non-random co-amplifications of genes at distant genomic loci were also observed. These findings provide basic information regarding the creation of a strategy for personalizing gastric cancer therapy, especially when using multiple kinase inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization

Kiyose

Nagura

Hong

et al. 2012

Pathology International

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“…In contrast, outcomes in women with metastases beyond the ovaries or with recurrent disease are extremely poor. Response rates of MCs to conventional ovarian cancer chemotherapy agents (platinum agent + taxanes) are low [7][8][9][10][11][12], and the efficacy of agents commonly used against gastrointestinal primaries (eg oxaliplatin, capecitabine, 5-fluorouracil) in MCs is still under investigation but appears unlikely to yield a significant improvement [13,14]. New treatment options are desperately needed for this histological subtype of EOC.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas

Anglesio

Kommoss

Tolcher

et al. 2012

The Journal of Pathology

172

138

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Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2-targeted treatment in a small series of women with recurrent HER2-amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non-amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2-overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2-targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.

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Targeting Src in mucinous ovarian carcinoma

Cited by 2 publications

References 10 publications

Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization

Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization

Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas

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