A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects

Sugawara, Etsuko; Kusano, Hironori; Yuba, Yoshiaki; Yorita, Kenji; Takeuchi, Kengo

doi:10.5114/pjp.2018.76693

Cited by 29 publications

(40 citation statements)

References 32 publications

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“…[25][26][27] Besides, there are several findings suggesting a close relationship between chromophobe RCCs and oncocytomas. 28 Loss of THSD7A expression was significantly associated with several adverse prognostic markers in RCCs. These correlations were even more pronounced in the subgroup of clear cell RCCs.…”

Section: R E S U L T Smentioning

confidence: 99%

THSD7A expression in human cancer

Stahl

Hoxha

Wiech

et al. 2017

Genes Chromosomes & Cancer

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We recently described a case of a Thrombospondin Type-1 Domain containing 7A (THSD7A) associated membranous nephropathy in a female patient who was synchronously suffering from a THSD7A-positive malignancy. We here investigated the role of THSD7A as a new potential tumor antigen by evaluating over 20 000 tissue spots in more than 70 different tumor entities by immunohistochemistry using tissue microarrays. THSD7A expression was highly variable in different neoplasias with differing staining patterns. Both gain and loss of THSD7A expression compared to expression status in non-tumor tissue were linked to tumor-specific markers in the different tumor entities and were of prognostic value. The potential role of THSD7A in tumor development and therapy needs further investigation.

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Section: R E S U L T Smentioning

confidence: 99%

THSD7A expression in human cancer

Stahl

Hoxha

Wiech

et al. 2017

Genes Chromosomes & Cancer

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“…Furthermore, the EML4-ALK (E13: A20 variant 1) fusion gene was revealed in these two patients, whose protumor effect and its effectiveness as a therapeutic target were tested in an animal xenograft model. There is no clinical trials or case report of an ALK inhibitor in treating ALK-rearranged RCC to date; however, ALK-RCC has been recently proposed and incorporated into the recent World Health Organisation Classification of Renal Tumours as a provisional entity (36); as ALK-targeted TKIs have shown impressive therapeutic efficacy in treating patients with ALK rearrangement in NSCLC and other cancers, it is possible that ALK inhibitor therapy will provide great benefit for patients with advanced stage ALK-rearranged ccRCC in the near future. Table II…”

Section: Discussionmentioning

confidence: 99%

Identification of anaplastic lymphoma kinase fusions in clear cell renal cell carcinoma

Chen

Bai³

et al. 2020

Oncol Rep

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As one of the most common types of renal cancer, clear cell renal cell carcinoma (ccRCC) in advanced stages constitutes a continued major challenge for uro-oncologists, as the identification of novel driver mutations and the development of novel targeted therapies against them remain an unmet need. Aberrations in anaplastic lymphoma kinase (ALK), a rational therapeutic target, as verified in lung cancer with ALK rearrangement, have been implicated in the pathogenesis of multiple human cancers. In the present study, we screened ALK expression in 87 pathologically defined ccRCCs via immunohistochemistry (IHC) using a newly developed rabbit anti-human ALK monoclonal antibody (clone D5F3). Four patients tested positive for ALK expression, as confirmed by IHC. Among them, 2 patients were further confirmed with fluorescence in situ hybridization (FISH) assay with the use of the Vysis LSI ALK dual color break-apart probe. Furthermore, we detected the existence of the echinoderm microtubule-associated protein-like 4/anaplastic lymphoma kinase (EML4-ALK) (E13:A20, variant 1) fusion gene in tumors from these two patients by using rapid amplification of cDNA ends (RACE)-coupled PCR sequencing and RT-PCR. Notably, we first showed that enforced EML4-ALK expression could significantly promote in vitro proliferation, clonogenic colony formation and apoptosis resistance in HK2 immortalized normal renal tubal epithelial cells and their in vivo outgrowth when injected into immunocompromised nude mice. Importantly, this pro-tumorigenic effect was completely abolished by the ALK-specific inhibitor crizotinib, indicating the potential effectiveness of ALK-specific inhibitors in treating ALK-rearranged ccRCC patients. Our data revealed that ALK fusions exist in adult ccRCC, providing a rationale for ALK inhibitor therapy in selected patients with ccRCC.

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“…New tRCCs, ALK‐rearranged RCCs, were also described in the 2016 WHO classification . In ALK‐rearranged RCCs, the ALK gene can fuse to the VCL , TPM3 , EML4 , HOOK1 or STRN gene . Most cases of MTSCC reportedly have Hippo pathway dysregulation .…”

Section: Molecular Features Of Nccrccsmentioning

confidence: 99%

“…The first‐line TT for metastatic Xp11 tRCC appears to be TKIs, especially SU. Various tRCCs have recently been reported . In the Vancouver Classification of Renal Cancer, Xp11 tRCC and t(6;11) RCC were combined to MiT family tRCC .…”

Section: Translocation Rccmentioning

confidence: 99%

Recent advances in the systemic treatment of metastatic non‐clear cell renal cell carcinomas

Ito

2019

Int J of Urology

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Abbreviations & Acronyms AA = anti-angiogenic ALK = anaplastic lymphoma kinase ARE = anti-oxidant responsive element ccRCC = clear cell renal cell carcinoma CDC = collecting duct carcinoma ChRCC = chromophobe renal cell carcinoma CR = complete response CTLA-4 = cytotoxic Tlymphocyte antigen 4 EV = everolimus FH = fumarate hydratase IMDC = International Metastatic Renal Cell Carcinoma Database Consortium INF-a = interferon-a IO drug = immuno-oncology drug ISUP = International Society of Urological Pathology LOH = loss of heterozygosity MET+ = MET mutation+ METÀ = MET mutationÀ MiT = microphthalmiaassociated transcription mOS = median overall survival mPFS = median progressionfree survival mPRCC = metastatic papillary renal cell carcinoma mRCC = metastatic renal cell carcinoma MSKCC = Memorial Sloan-Kettering Cancer Center mTORi = mammalian target of rapamycin inhibitor MTSCC = mutinous tubular and spindle cell carcinoma NA = not availableAbstract: There is still no standard treatment for non-clear cell renal cell carcinomas. Sunitinib is the most examined drug because of its effectiveness in retrospective studies and clinical trials, and is the preferred first-line drug in the National Comprehensive Cancer Network guideline. Temsirolimus is an option as a first-line drug, especially for poor-risk non-clear cell renal cell carcinoma patients. Everolimus, pazopanib, axitinib and nivolmab might also be viable options. Clinical trials are still required to gather evidence regarding non-clear cell renal cell carcinoma treatment. Because each non-clear cell renal cell carcinoma has a different genetic background and molecular features, specific treatment for each non-clear cell renal cell carcinoma should be established. From the results of a Japanese multicenter study, tyrosine kinase inhibitors might be better used for metastatic papillary renal cell carcinoma in both first-and second-line settings. Both tyrosine kinase inhibitors and mammalian target of rapamicin inhibitors are effective for metastatic chromophobe renal cell carcinoma, but the preferred first-line drug has not been determined. Platinum-based chemotherapies are currently recommended for metastatic collecting duct carcinoma, and anti-angiogenic drugs are effective in some cases. Tyrosine kinase inhibitors, especially sunitinib, appear to be effective for X11.2 translocation renal cell carcinoma among the microphthalmia-associated transcription family of translocation renal cell carcinomas. Evidence is still lacking regarding the treatment for other rare non-clear cell renal cell carcinomas. Appropriate sequential therapies using antivascular endothelial growth factor therapies, mammalian target of rapamicin inhibitors and immuno-oncology drugs should be established for each nonclear cell renal cell carcinoma. None declared. References 1 Ito K. Recent advances in the systemic treatment of metastatic non-clear cell renal cell carcinoma. Int. J. Urol. 2019; 26: 868-77. 2 Teishima J, Inoue S, Hayashi T, Matsubara A. Current status of prognostic factors in ...

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A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects

Cited by 29 publications

References 32 publications

THSD7A expression in human cancer

THSD7A expression in human cancer

Identification of anaplastic lymphoma kinase fusions in clear cell renal cell carcinoma

Recent advances in the systemic treatment of metastatic non‐clear cell renal cell carcinomas

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