In vitro radiosensitisation by trabectedin in human cancer cell lines

Romero, Jesús; Zapata, I.; Cordoba, Shaun-Paul; Jimeno, J.; López-Martín, José A.; Tercero, Juan Carlos; Torre, Alejandro de la; Vargas, Juan A.; Molerón, R.; Sánchez‐Prieto, Ricardo

doi:10.1016/j.ejca.2008.04.013

Cited by 26 publications

(24 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To evaluate the cytotoxic effects of artemisinin and its derivates on A549 cells and get the IC 10 values to judge the radiosensitization according to previous report [13], the viabilities of cells treated with different concentrations (ranging from 50 to 1600 μM) of artemisinin and its derivates were measured using MTT test. The results showed that artemisinin and its derivates reduced cell survival in a dose-dependent manner.…”

Section: Resultsmentioning

confidence: 99%

Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

Zhao

Jiang

et al. 2011

International Immunopharmacology

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

Zhao

Jiang

et al. 2011

International Immunopharmacology

View full text Add to dashboard Cite

“…The unique molecular function of trabectedin potentially influences delayed response to the treatment besides tumor histology. Trabectedin is known to show antitumor activity by inhibiting tumor cell DNA repair and by inducing apoptosis 12 . Besides it, Galmarini et al suggested that the effect of trabectedin on the tumor microenvironment was another mechanism leading to tumor size diminishment 13 .…”

Section: Discussionmentioning

confidence: 99%

Time lapse analysis of tumor response in patients with soft tissue sarcoma treated with trabectedin: A pooled analysis of two phase II clinical trials

et al. 2020

View full text Add to dashboard Cite

The time course of the response to each drug is important to avoid inappropriate termination of treatment by misjudging tumor progression; however, little is known about soft tissue sarcoma (STS) regarding this matter. This study aimed to perform a time-lapse analysis of tumor response in patients with STS treated with trabectedin from 2 phase II clinical trials.We examined 66 patients with translocation-related sarcoma registered in 2 Japanese phase II clinical trials. All patients previously received standard therapy before the administration of trabectedin at 1.2 mg/m 2 every 3 weeks. Imaging evaluation was performed according to the study protocol. The sum of the maximum diameters of the target lesions was calculated and analyzed over time.Among the 66 patients, 9 (13.6%) showed partial response (PR) to trabectedin. Histological diagnoses of these 9 responders comprised 6 myxoid liposarcoma, 2 synovial sarcoma, and a | 3657 ENDO Et al. Primary lesion Lower limbs, n (%) 36 (54.5) 21 (56.8) 15 (51.7) Abdomen/pelvis, n (%) 7 (10.6) 3 (8.1) 4 (13.8) Face, n (%) 5 (7.6) 1 (2.7) 4 (13.8) Intrathoracic, n (%) 3 (4.5) 3 (8.1) 0 (0.0) Neck, n (%) 3 (4.5) 2 (5.4) 1 (3.4) Retroperitoneum, n (%) 3 (4.5) 1 (2.7) 2 (6.9) Other, n (%) 9 (13.6) 6 (16.2) 3 (10.3) Site by independent radiologic image assessment* Lung, n (%) 43 (65.2) 25 (67.6) 18 (62.1) Peritonea, n (%) 22 (33.3) 12 (32.4) 10 (34.5) Lymph node, n (%) 20 (30.3) 11 (29.7) 9 (31.0) Pleura, n (%) 19 (28.8) 11 (29.7) 8 (27.6) Muscle, n (%) 16 (24.2) 9 (24.3) 7 (24.1) Bone, n (%) 16 (24.2) 11 (29.7) 5 (17.2) Other, n (%) 15 (22.7) 10 (27.0) 5 (17.2) Sum of the diameters of target lesions by independent radiologic image assessment (mm) Median (range) 97.65 [10.0, 443.9] 91.70 [10.0, 443.9] 134.20 [25.7, 422.7] Number of prior regimens of systemic anticancer agents Median (range) 1.0 [0,4] 1.0 [0,3] 2.0 [0,4] Abbreviation: PS, Performance Status. *Multiple answers allowed.

show abstract

“…Accordingly, it was shown that cells in the S‐phase are most vulnerable with regard to heat . An arrest of cells in the G2/M phase induced by trabectedin alone was discussed with regard to different degrees of radiosensitization . Radiosensitivity of cells changes within progression of the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

“…34 An arrest of cells in the G2/M phase induced by trabectedin alone was discussed with regard to different degrees of radiosensitization. 35,36 Radiosensitivity of cells changes within progression of the cell cycle. While cells in the S-phase are particularly radioresistant, cells in the G2/M phase are considered as the most radiosensitive.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia adds to trabectedin effectiveness and thermal enhancement is associated with BRCA2 degradation and impairment of DNA homologous recombination repair

Harnicek

Kampmann

Lauber

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

The tetrahydroisoquinoline trabectedin is a marine compound with approved activity against human soft-tissue sarcoma. It exerts antiproliferative activity mainly by specific binding to the DNA and inducing DNA double-strand breaks (DSB). As homologous recombination repair (HRR)-deficient tumors are more susceptible to trabectedin, hyperthermia-mediated on-demand induction of HRR deficiency represents a novel and promising strategy to boost trabectedin treatment. For the first time, we demonstrate enhancement of trabectedin effectiveness in human sarcoma cell lines by heat and characterize cellular events and molecular mechanisms related to heat-induced effects. Hyperthermic temperatures (41.8 or 438C) enhanced significantly trabectedin-related clonogenic cell death and G2/M cell cycle arrest followed by cell type-dependent induction of apoptosis or senescence. Heat combination increased accumulation of cH2AX foci as key marker of DSBs. Expression of BRCA2 protein, an integral protein of the HRR machinery, was significantly decreased by heat. Consequently, recruitment of downstream RAD51 to cH2AX-positive repair foci was almost abolished indicating relevant impairment of HRR by heat. Accordingly, enhancement of trabectedin effectiveness was significantly augmented in BRCA2-proficient cells by hyperthermia and alleviated in BRCA2 knockout or siRNA-transfected BRCA2 knockdown cells. In peripheral blood mononuclear cells isolated from sarcoma patients, increased numbers of nuclear cH2AX foci were detected after systemic treatment with trabectedin and hyperthermia of the tumor region. The findings establish BRCA2 degradation by heat as a key factor for a novel treatment strategy that allows targeted chemosensitization to trabectedin and other DNA damaging antitumor drugs by on-demand induction of HRR deficiency.Trabectedin (Yondelis V R ) is a DNA-intercalating anticancer drug originally isolated from the sea squirt Ecteinascidia turbinata. The drug is established for the treatment of advanced soft-tissue sarcoma after failure of anthracyclines and ifosfamide as well as for the treatment of platinum-sensitive ovarial carcinoma in combination with liposomal doxorubicin. In sarcoma, trabectedin usually induces high rates of tumor growth arrest. In a worldwide-expanded access program investigating 1,895 patients, stable disease was reported in 43% and overall survival was 11.9 months. Unfortunately, treatment response with relevant tumor shrinkage was only seen in 5%. 1 Given the worse prognosis of advanced sarcoma, there is urgent need to improve treatment. Enhancing antitumor efficacy of trabectedin by a local treatment seems to be a promising strategy.

show abstract

In vitro radiosensitisation by trabectedin in human cancer cell lines

Cited by 26 publications

References 35 publications

Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

Time lapse analysis of tumor response in patients with soft tissue sarcoma treated with trabectedin: A pooled analysis of two phase II clinical trials

Hyperthermia adds to trabectedin effectiveness and thermal enhancement is associated with BRCA2 degradation and impairment of DNA homologous recombination repair

Contact Info

Product

Resources

About