Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma

Moreno‐Acosta, Pablo; Vallard, Alexis; Carrillo, Schyrly; Gamboa, Óscar; Romero‐Rojas, Alfredo; Molano, Mónica; Acosta, Jinneth; Mayorga, Diana; Rancoule, C.; Garcia, Max-Adrien; Mestre, Martha Cotes; Magné, Nicolas

doi:10.1186/s13014-017-0856-2

Cited by 39 publications

(37 citation statements)

References 29 publications

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“…44 In cervical cancer patients, the increased expression of hTERT is related to radiation resistance and poor prognosis. 45 In the current study, we treated cervical cancer cells with HEK293-derived exosomes containing miR-22 and observed a reduced hTERT expression and increased radiosensitivity of the recipient cervical cancer cells in vitro. Although the present study has a limitation in that the role of exosomal miR-22 was evaluated only in in vitro experiments, this is the first report to show that exosomal miR-22 induced radiosensitization through hTERT reduction.…”

Section: Discussionmentioning

confidence: 64%

The therapeutic potential of exosomal miR-22 for cervical cancer radiotherapy

Konishi

Hayashi

Taniguchi

et al. 2020

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 64%

The therapeutic potential of exosomal miR-22 for cervical cancer radiotherapy

Konishi

Hayashi

Taniguchi

et al. 2020

Cancer Biology & Therapy

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“…16 In addition, it is possible to treat some cervical cancers that develop resistance to radiation therapy. 16 Furthermore, when pelvic recurrence occurs, it can be successfully cured by radiation therapy in those patients who are primarily treated with radical hysterectomy alone, whereas salvage surgery in a radiated pelvis is challenging and associated with higher surgical complications such as permanent ostomies for colon and urinary bladder. 17 Following primary radical hysterectomy, adjuvant treatment is indicated depending on pathologic risk factors and disease stage.…”

Section: Original Research Discussionmentioning

confidence: 99%

“…One of the advantages of primary surgery is that one can obtain a histopathologic outcome associated with risk factors and final surgical staging from the surgical specimen. 16 In addition, it is possible to treat some cervical cancers that develop resistance to radiation therapy. 16 Furthermore, when pelvic recurrence occurs, it can be successfully cured by radiation therapy in those patients who are primarily treated with radical hysterectomy alone, whereas salvage surgery in a radiated pelvis is challenging and associated with higher surgical complications such as permanent ostomies for colon and urinary bladder.…”

Section: Discussionmentioning

confidence: 99%

The upper limit of optimal tumor size in patients with FIGO 2018 stage IB2 cervical cancer undergoing radical hysterectomy

Kim

Suh

Kim

et al. 2020

Int J Gynecol Cancer

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ObjectivePatients who undergo radical hysterectomy may require postoperative adjuvant radiotherapy, and all efforts should be made to reduce dual therapy in such patients. The aim of this study was to determine the optimal upper limit of tumor size in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB2 cervical cancer who undergo radical hysterectomy.MethodsWe retrospectively reviewed the records of 114 patients with FIGO 2018 stage IB2 cervical cancer who underwent primary surgery either with (n=55) or without (n=59) adjuvant radiotherapy from June 2004 to December 2018. The inclusion criteria were as follows: women diagnosed with stage IB2 cervical cancer; primary radical surgery with pelvic lymph node dissection with or without para-aortic lymph node dissection; and patients treated with or without postoperative adjuvant radiation therapy, concurrent chemoradiation therapy, or chemotherapy. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal tumor size cut-off value. The optimal tumor size cut-off value was determined by the maximum sum of sensitivity and specificity.ResultsThere were 55 and 59 patients treated with or without adjuvant therapy, respectively, after radical hysterectomy. Age, histologic type, and pelvic and para-aortic lymph node sampling/dissection status were similar between each group. The number of patients with a tumor size <2.7 cm and ≥2.7 cm was 39 and 75, respectively. The decision for adjuvant treatment after radical hysterectomy in patients with stage IB2 cervical cancer was influenced by intermediate risk factors (lymphovascular space invasion, 23.7% vs 76.4%, p<0.001; deep 1/3 of invasion, 16.9% vs 61.8%, p<0.001) and high risk factors (lymph node metastasis, 0% vs 40.0%, p<0.001; involvement of parametrium, 1.7% vs 16.4%, p=0.007). According to the ROC curve results considering the best sensitivity and specificity, the optimal cut-off value of tumor size for predicting adjuvant treatment was 2.7 cm (sensitivity 0.85, specificity 0.52). The number of patients with a tumor size <2.7 cm and ≥2.7 cm was 39 (34.2%) and 75 (65.8%), respectively. No significant differences were observed in the progression-free survival (p=0.22) and overall survival (p=0.28) rates between tumor size smaller than 2.7 cm and larger than 2.7 cm.ConclusionsA cervical tumor larger than 2.7 cm before radical surgery in stage IB2 may predispose to potential complications from combining radical hysterectomy and concurrent chemoradiation,. We consider that concurrent chemoradiation therapy is a more appropriate choice for tumor size over 2.7 cm per the revised FIGO 2018 criteria for stage IB2 cervical cancer.

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“…Regardless of the location of IGF-IR, high levels of IGF-IR are associated with high tumor stage, HPV negativity, and short overall survival [42]. Overexpression of IGF-IRβ was correlated with a decreased survival in patients with cervical carcinoma [43]. Except for the levels of IGF-IR, the IGF-activated gene transcription signature is strongly associated with poor prognosis in breast cancer patients [38].…”

Section: Igfs and Their Receptorsmentioning

confidence: 99%

Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy

et al. 2020

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Insulin-like growth factors (IGFs) play important roles in mammalian growth, development, aging, and diseases. Aberrant IGFs signaling may lead to malignant transformation and tumor progression, thus providing the rationale for targeting IGF axis in cancer. However, clinical trials of the type I IGF receptor (IGF-IR)-targeted agents have been largely disappointing. Accumulating evidence demonstrates that the IGF axis not only promotes tumorigenesis, but also confers resistance to standard treatments. Furthermore, there are diverse pathways leading to the resistance to IGF-IR-targeted therapy. Recent studies characterizing the complex IGFs signaling in cancer have raised hope to refine the strategies for targeting the IGF axis. This review highlights the biological activities of IGF-IR signaling in cancer and the contribution of IGF-IR to cytotoxic, endocrine, and molecular targeted therapies resistance. Moreover, we update the diverse mechanisms underlying resistance to IGF-IR-targeted agents and discuss the strategies for future development of the IGF axis-targeted agents.

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Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma

Cited by 39 publications

References 29 publications

The therapeutic potential of exosomal miR-22 for cervical cancer radiotherapy

The therapeutic potential of exosomal miR-22 for cervical cancer radiotherapy

The upper limit of optimal tumor size in patients with FIGO 2018 stage IB2 cervical cancer undergoing radical hysterectomy

Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy

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