Thymic Malignancies: From Clinical Management to Targeted Therapies

Kelly, Ronan J.; Petrini, Iacopo; Rajan, Arun; Wang, Yisong; Giaccone, Giuseppe

doi:10.1200/jco.2011.36.0487

Cited by 135 publications

(139 citation statements)

References 97 publications

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“…3,4 A crucial advance in TET management could derive from the identification of new molecular biomarkers related to these neoplasms able to improve diagnosis, prognosis and treatment planning. 5,6 MicroRNA expression is tissue-specific and highly regulated according to the cells developmental lineage and stage. 7 Several lines of evidence indicate that miRNAs might be differentially expressed in cancer cells, in which they form unique expression patterns or signatures.…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

Bellissimo

Russo

Ganci³

et al. 2015

Cancer Biology & Therapy

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Thymic epithelial cells give rise to both thymoma and thymic carcinoma. A crucial advance in thymic epithelial tumors (TET) management may derive from the identification of novel molecular biomarkers able to improve diagnosis, prognosis and treatment planning.In a previous study, we identified microRNAs that were differentially expressed in tumor vs normal thymic tissues. Among the microRNAs resulted upregulated in TET tissues, we evaluated miR-21-5p, miR-148a-3p, miR-141-3p, miR-34b-5p, miR-34c-5p, miR-455-5p as blood plasma circulating non-invasive biomarkers for TET management.We firstly report that the expression levels of specific onco-miRNAs, that we found upregulated in the blood plasma collected from TET patients at surgery, resulted significantly reduced in follow-up samples.This pilot study suggests that circulating miR-21-5p and miR-148a-3p could represent novel non-invasive biomarkers to evaluate the efficacy of therapy and the prognosis of TET.

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Section: Introductionmentioning

confidence: 99%

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

Bellissimo

Russo

Ganci³

et al. 2015

Cancer Biology & Therapy

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“…Development of targeted therapy for TETs has been hampered by insufficient knowledge of their tumor biology and scarcity of targetable oncogenic driver abnormalities (28). In this study, we took an unconventional targeted approach to explore a potential therapeutic strategy for TETs by targeting XPO1.…”

Section: Discussionmentioning

confidence: 99%

“…TETs are rare tumors originated from thymic epithelia, and therapeutic options are limited for advanced-stage diseases (26)(27)(28). Development of targeted therapy for TETs has been hampered by insufficient knowledge of their tumor biology and scarcity of targetable oncogenic driver abnormalities (28).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of XPO1 Inhibition in Thymic Epithelial Tumors

Conforti¹,

Zhang²,

Rao³

et al. 2017

Cancer Res

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Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins, including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells, and induces p53-dependent and -independent antitumor activity in vitro. Selinexor suppressed the growth of TET xenograft tumors in athymic nude mice via inhibition of cell proliferation and induction of apoptosis. Loss of p53 activity or amplification of XPO1 may contribute to resistance to XPO1 inhibitor in TET. Using mass spectrometry-based proteomics analysis, we identified a number of proteins whose abundances in the nucleus and cytoplasm shifted significantly following selinexor treatment in the TET cells. Furthermore, we found that XPO1 was highly expressed in aggressive histotypes and advanced stages of human TET, and high XPO1 expression was associated with poorer patient survival. These results underscore an important role of XPO1 in the pathogenesis of TET and support clinical development of the XPO1 inhibitor for the treatment of patients with this type of tumors. Cancer Res; 77(20); 5614-27. Ó2017 AACR.

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“…For the patients with inoperable or recurrent diseases, chemotherapy is the alternative treatment. 8 If the tumor is not resectable after neoadjuvant chemotherapy, additional chemotherapy and/or radiotherapy can be used. Standard chemotherapy for thymic carcinomas remains undefined.…”

Section: Discussionmentioning

confidence: 99%

Isolated splenic metastasis from a thymic carcinoma: A case report

Chen

Meng

Zhao

et al. 2016

Cancer Biology & Therapy

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Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases.

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Thymic Malignancies: From Clinical Management to Targeted Therapies

Cited by 135 publications

References 97 publications

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

Therapeutic Effects of XPO1 Inhibition in Thymic Epithelial Tumors

Isolated splenic metastasis from a thymic carcinoma: A case report

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