Current controversies in radiotherapy for breast cancer

Krug, David; Baumann, René; Budach, Wilfried; Dunst, Jürgen; Feyer, Petra; Fietkau, Rainer; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Souchon, Rainer; Wenz, Frederik; Sauer, Rolf

doi:10.1186/s13014-017-0766-3

Cited by 42 publications

(31 citation statements)

References 55 publications

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“…To achieve better therapeutic effect, we next experimented with four fractionated doses of 2 Gy IR which more closely mirrored the clinical IR treatment used in breast cancer [36]. VPA or HPTA were administrated before, during, and after IR treatment (Figure.…”

Section: Hpta Exhibits Radiosensitizing Properties To Ir Treatment Inmentioning

confidence: 99%

2-hexyl-4-pentynoic acid (HPTA), a novel radiosensitizer to breast cancer cells through increasing the instability of DNA repair proteins

Cai

Lim

Liu

et al. 2020

Preprint

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Background Breast cancer is one of the most common malignant tumors in the world which is the main cause of cancer death for women. Radiotherapy is the main treatment. Although some drugs have been found to enhance the effect of radiotherapy, there are also obvious deficiencies. Therefore, recent applied clinical research has been focusing on locating a suitable radiosensitizer to breast cancer radiotherapy. Methods MTT, clonogenic survival assays, comet assays, immunofluorescence and western blot analyses were used to detect the effect of VPA / HPTA on DNA damage induced by radiotherapy for breast cancer through a variety of cell models( MCF7, EUFA423, HCC1937, DMBA-induced rat breast cancer-derived primary culture cell and DMBA-induced transformed human normal breast cell line). At the same time, flow cytometry, immunofluorescence and western blot analyses were used to investigate the effect of VPA / HPTA on DNA damage repair induced by radiation. In vivo experiment, the effect of HPTA as radiosensitizer was investigated by DMBA-induced breast cancer in rats. Finally, the possible mechanism of HPTA acting on target protein was proved by cycloheximide chase experiment. Results In this study, a derivative of valproic acid (VPA), 2-hexyl-4-pentynoic acid (HPTA), was demonstrated for the first time that low concentration of HPTA (15 µM) has radiosensitizing properties to breast cancer cells by multiple working models of breast cancer cell lines (in vivo), equivalent to a high concentration of VPA (500 µM). Mechanistic investigations revealed that HPTA induced radiosensitivity through inhibiting the BRCA1-Rad51-mediated homologous recombination pathway. These results were further manifested in breast cancer animal model (in vitro). Most importantly, our study found that HPTA influenced the stability of BRCA1 and Rad51 proteins via shorting their half-life. Conclusions Our findings support the proposition HPTA as an alternate, safe and effective radiosensitizer to tumor cells. Targeting BRCA1-Rad51-mediated homologous recombination pathway through HPTA may be a rational strategy to improve the radiotherapeutic efficacy of breast cancer.

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Section: Hpta Exhibits Radiosensitizing Properties To Ir Treatment Inmentioning

confidence: 99%

2-hexyl-4-pentynoic acid (HPTA), a novel radiosensitizer to breast cancer cells through increasing the instability of DNA repair proteins

Cai

Lim

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Breast cancer is the most common malignancy among women and the second leading cause of cancer deaths in women in the United States. 1 Locoregional treatment of breast cancer with radiation therapy has evolved over the past several decades, 2 which has been a critical component of the multimodal management of invasive breast cancer. 3 However, development of radioresistance becomes one of the most critical obstacles in cancer radiotherapy.…”

Section: ■ Introductionmentioning

confidence: 99%

Targeted Profiling of Heat Shock Proteome in Radioresistant Breast Cancer Cells

Miao

Fan

Huang

et al. 2018

Chem. Res. Toxicol.

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Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Radioresistance remains one of the most critical barriers in radiation therapy for breast cancer. In this study, we employed a parallel-reaction monitoring (PRM)-based targeted proteomic method to examine the reprogramming of the heat shock proteome during the development of radioresistance in breast cancer. In particular, we investigated the differential expression of heat shock proteins (HSPs) in two pairs of matched parental/radioresistant breast cancer cell lines. We were able to quantify 43 and 42 HSPs in the MCF-7 and MDA-MB-231 pairs of cell lines, respectively. By analyzing the commonly altered proteins, we found that several members of the HSP70 and HSP40 subfamilies of HSPs exhibited substantially altered expression upon development of radioresistance. Moreover, the expression of HSPB8 is markedly elevated in the radioresistant lines relative to the parental MCF-7 and MDA-MB-231 cells. Together, our PRM-based targeted proteomics method revealed the reprogramming of the heat shock proteome during the development of radioresistance in breast cancer cells and offered potential targets for sensitizing breast cancer cells toward radiation therapy.

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“…Considerable controversy remains with respect to the use of radiotherapy for breast cancer (6). Firstly, it can be difficult to predict the patient's sensitivity to radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Developing a radiosensitivity gene signature for Caucasian patients with breast cancer

Jiang

Jian

et al. 2018

Oncol Rep

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Adjuvant radiotherapy is an important clinical treatment option for patients with breast cancer. However, for Caucasian patients, the clinical benefit of adjuvant radiotherapy can differ from African‑American patients with respect to the overall survival. The goal of the current study was to develop a gene signature and to pre‑identify patients likely to benefit from radiotherapy. Using publicly available breast cancer data from The Cancer Genome Atlas, a new cross‑validation procedure was proposed for developing a gene signature and predicting radiosensitive patients. The results demonstrated that the predicted radiosensitive patients who received radiotherapy exhibited a significantly better survival, while the effect of radiotherapy was not significant for predicted non‑radiosensitive patients. Further hierarchical cluster analysis revealed that the predicted sensitivity for each patient corresponded closely to the results of the cluster analysis. Collectively, the findings of the current study demonstrated that a radiosensitive molecular signature can be used to identify radiosensitive Caucasian patients with breast cancer.

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Current controversies in radiotherapy for breast cancer

Cited by 42 publications

References 55 publications

2-hexyl-4-pentynoic acid (HPTA), a novel radiosensitizer to breast cancer cells through increasing the instability of DNA repair proteins

2-hexyl-4-pentynoic acid (HPTA), a novel radiosensitizer to breast cancer cells through increasing the instability of DNA repair proteins

Targeted Profiling of Heat Shock Proteome in Radioresistant Breast Cancer Cells

Developing a radiosensitivity gene signature for Caucasian patients with breast cancer

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