Faculty Profiles - SHIEN Tadahiko

A single-arm confirmatory study to evaluate the efficacy of nonsurgical therapy for HER2-positive early breast cancer with clinical complete response after primary systemic therapy (JCOG1806: AMATERAS-BC study).

Tomomi Fujisawa, Tadahiko Shien, Hiroji Iwata, Hideo Shigematsu, Taro Shibata, Keita Sasaki, Yuko Takahashi

JOURNAL OF CLINICAL ONCOLOGY 39 ( 15 ) 2021.5

A Multicenter Study of Docetaxel at a Dose of 100 mg/m2 in Japanese Patients with Advanced or Recurrent Breast Cancer.

Taizo Hirata, Shinji Ozaki, Masahiro Tabata, Takayuki Iwamoto, Shiro Hinotsu, Akinobu Hamada, Takayuki Motoki, Tomohiro Nogami, Tadahiko Shien, Naruto Taira, Junji Matsuoka, Hiroyoshi Doihara

Internal medicine (Tokyo, Japan) 60 ( 8 ) 1183 - 1190 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective This study examined the pharmacokinetics, safety and anti-tumor activity of docetaxel at a dose of 100 mg/m2 in Japanese patients with advanced or recurrent breast cancer. Methods Japanese patients with advanced or recurrent breast cancer received docetaxel at a dose of 100 mg/m2 intravenously every three weeks. The pharmacokinetics were assessed during the first cycle. The patients were allowed to receive supportive care drugs based on the indications and dosages in Japan. Results Six eligible patients aged 39-65 years old and 27 treatment cycles were analyzed. All patients experienced one or more adverse events (AEs). The common AEs were neutropenia, thrombocytopenia, alopecia, rash, diarrhea, neuropathy (sensory), fatigue, nausea, fever, hypoalbuminemia, alanine transaminase (ALT) increased, constipation, and taste alteration. Grade 3 or 4 AEs included neutropenia, leukopenia, anemia, lymphopenia, decreased appetite, γ-glutamyl transpeptidase (GTP) increased, aspartate transaminase (AST) increased, ALT increased, hypertension and cellulitis which were all reversible. There were no cases of febrile neutropenia, serious AEs or deaths. The median number of cycles was six. Dose reductions were not observed and most cycles were administered at their intended doses. No complete response and three partial responses were observed in four assessable patients with evaluable lesions. The maximum concentration and area under the blood concentration-time curve were 3,417.5 ng/mL and 4.35 μg・hr/mL (mean), respectively. Conclusion Docetaxel at a dose of 100 mg/m2 was tolerable with acceptable safety profiles and effective for Japanese patients with advanced or recurrent breast cancer with appropriate supportive therapies, and pharmacokinetic (PK) profiles which corresponded approximately with the findings of previous clinical studies.

DOI： 10.2169/internalmedicine.5089-20

Risk factors of local recurrence following implant-based breast reconstruction in breast cancer patients. International journal

Miwa Fujihara, Rie Yamasaki, Mitsuya Ito, Tadahiko Shien, Reina Maeda, Takanori Kin, Ayako Ueno, Yukiko Kajiwara, Kensuke Kawasaki, Kouichi Ichimura, Hiroya Mihara, Naritaka Kimura, Shoichiro Ohtani

BMC women's health 21 ( 1 ) 147 - 147 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC

BACKGROUND: The number of patients desiring implant-based breast reconstruction has been increasing. While local recurrence is observed in patients with breast reconstruction, only a few reports have focused on the risk factors for local recurrence and the prognosis after developing local recurrence. METHODS: We analyzed 387 patients who underwent implant-based breast reconstruction during the period from 2004 to 2017 in Hiroshima City Hospital. We retrospectively examined the risk factors for local recurrence and the outcomes of patients developing such recurrence after implant-based breast reconstruction. RESULTS: The median follow-up time was 59 months. The local recurrence rate was 3.1% (n = 12). The most common reason for detecting local recurrence was a palpable mass. Four patients with local recurrence had recurrence involving the skin just above the primary lesion and needle biopsy tract. All patients with local recurrence received surgery and systemic therapy and most patients received radiation therapy, all have remained free of new recurrence to date. Multivariate analysis showed lymphatic vessel invasion (HR, 6.63; 95% CI, 1.40-31.36; p = 0.017) and positive or < 2 mm vertical margin (HR, 9.72; 95%CI, 1.23-77.13; p = 0.047) to be associated with significantly increased risk of local recurrence. CONCLUSIONS: The risk factors for local recurrence following implant-based breast reconstruction were lymphatic vessel invasion and positive or < 2 mm vertical margin. Removal of the skin just above the primary lesion and needle biopsy tract and adjuvant radiation therapy might improve local outcomes. Patients with local recurrence following implant-based breast reconstruction appear to have good outcomes with appropriate treatment.

DOI： 10.1186/s12905-021-01287-4

Current Status of Advance Care Planning and End-of-life Communication for Patients with Advanced and Metastatic Breast Cancer. International journal

Yasuaki Sagara, Masanori Mori, Sena Yamamoto, Keiko Eguchi, Tsuguo Iwatani, Yoichi Naito, Takahiro Kogawa, Kiyo Tanaka, Haruru Kotani, Hiroyuki Yasojima, Yukinori Ozaki, Emi Noguchi, Minoru Miyasita, Naoto Kondo, Naoki Niikura, Masakazu Toi, Tadahiko Shien, Hiroji Iwata

The oncologist 26 ( 4 ) e686-e693 2021.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Advance care planning (ACP) is a process that supports adults in understanding and sharing their personal values, life goals, and preferences regarding future medical care. We examined the current status of ACP and end-of-life (EOL) communication between oncologists and patients with metastatic breast cancer. MATERIALS AND METHODS: We conducted a survey among 41 institutions that specialize in oncology by using an online tool in October 2019. Participants (118 physicians) from 38 institutions completed a 39-item questionnaire that measured facility type and function; physicians' background and clinical approach, education about EOL communication, and understanding about ACP; and the current situation of ACP and EOL discussions. RESULTS: Ninety-eight responses concerning physicians' engagement in ACP with patients were obtained. Seventy-one (72%) answered that they had engaged in ACP. Among these, 23 (33%) physicians used a structured format to facilitate the conversation in their institutions, and only 6 (8%) settled triggers or sentinel events for the initiation of ACP. In the multivariable analysis, only the opportunity to learn communication skills was associated with physicians' engagement with ACP (odds ratio: 2.8, 95% confidence interval: 1.1-7.0). The frequency and timing of communication about ACP and EOL care with patients substantially varied among the oncologists. Communication about patients' life expectancy was less frequent compared with other topics. CONCLUSION: The opportunity to improve EOL communication skills promoted physicians' engagement with ACP among patients with metastatic/advanced breast cancer. However, there were still substantial variabilities in the method, frequency, and timing of ACP and EOL communication among the oncologists. IMPLICATIONS FOR PRACTICE: This study found that the opportunity to improve end-of-life (EOL) communication skills promoted physicians' engagement in advance care planning (ACP) among patients with metastatic/advanced breast cancer. All oncologists who treat said patients are encouraged to participate in effective education programs concerning EOL communication skills. In clinical practice, there are substantial variabilities in the method, frequency, and timing of ACP and EOL communication among oncologists. As recommended in several clinical guidelines, the authors suggest a system that identifies patients who require conversations about their care goals, a structured format to facilitate the conversations, and continuous measurement for improving EOL care and treatment.

DOI： 10.1002/onco.13640

岡山大学外科GRAPESの活動とこれから

竹原裕子, 吉田龍一, 溝尾妙子, 剱持礼子, 小林純子, 新田薫, 工藤由里絵, 元木崇之, 片岡正文, 池田宏国, 菊池覚次, 黒田新士, 枝園忠彦, 山根正修, 小谷恭弘, 大澤晋, 土井原博義, 豊岡伸一, 笠原慎悟, 藤原俊義

日本外科学会定期学術集会抄録集 121回 SF - 5 2021.4

Current status of PD-1/PD-L1 blockade immunotherapy in breast cancer. International journal

Emi Noguchi, Tadahiko Shien, Hiroji Iwata

Japanese journal of clinical oncology 51 ( 3 ) 321 - 332 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Over the past 10 years, immunotherapy with immune checkpoint inhibitors has revolutionized the management of various cancers. However, immunotherapy in breast cancer has not been successful. Breast cancer has long been recognized as an immunologically 'cold' tumor, although a higher frequency of tumor-infiltrating lymphocytes present in certain subtypes and an association between tumor-infiltrating lymphocytes and favorable prognosis have been reported. In March 2019, the combination of atezolizumab and nanoparticle albumin-bound paclitaxel was granted accelerated approval in the United States for the treatment of programmed death-ligand 1-positive advanced or metastatic triple-negative breast cancer. This finally opened the door for immune checkpoint blockade therapy for breast cancer. Several clinical trials have been conducted using different combinations of immune checkpoint inhibitors and chemotherapy or targeted agents in various treatment settings for metastatic breast cancer and early-stage breast cancer. In this review, we summarize recent advances in immune checkpoint blockade therapy and predictive biomarkers in breast cancer.

DOI： 10.1093/jjco/hyaa230

Prospective observational study estimating willingness-to-pay for breast cancer treatments through contingent valuation method in Japanese breast cancer patients (JCOG1709A). International journal

Tsuguo Iwatani, Fumikata Hara, Tadahiko Shien, Keita Sasaki, Hiroshi Katayama, Haruhiko Fukuda, Takeru Shiroiwa, Hiroji Iwata

Japanese journal of clinical oncology 51 ( 3 ) 498 - 503 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

In April 2016, the Japanese government introduced health technology assessment as a response to rising medical expenses due to 'medical innovation'. This study investigates how Japanese breast cancer patients who received treatment in Japan consider the financial value (willingness-to-pay; WTP) for their life and health by using the contingent valuation method (CVM) prospectively. First, 168 patients (84 primary breast cancer patients and 84 metastatic breast cancer patients) were pre-examined their WTP with dichotomous-choice method survey form. Next, 1,596 patients (798 primary breast cancer patients and 798 metastatic breast cancer patients) will be surveyed to their WTP for hypothetical scenarios in CVM. Based on our results, we will construct an evaluation axis from the patients' viewpoint for the cost-effectiveness of clinical trials to establish standard treatments for breast cancer. We believe this research can contribute to create a meaningful healthcare system for patients, clinicians, industries, and healthcare policymakers.

DOI： 10.1093/jjco/hyaa241

Nuclear grade and comedo necrosis of ductal carcinoma in situ as histopathological eligible criteria for the Japan Clinical Oncology Group 1505 trial: an interobserver agreement study. International journal

Hitoshi Tsuda, Masayuki Yoshida, Futoshi Akiyama, Yasuyo Ohi, Keiichi Kinowaki, Nobue Kumaki, Yuzuru Kondo, Akihisa Saito, Eiichi Sasaki, Rieko Nishimura, Satoshi Fujii, Keiichi Homma, Rie Horii, Yuya Murata, Makiko Itami, Sabine Kajita, Hiroyuki Kato, Masafumi Kurosumi, Takashi Sakatani, Shigeki Shimizu, Kohei Taniguchi, Sadafumi Tamiya, Harumi Nakamura, Chizuko Kanbayashi, Tadahiko Shien, Hiroji Iwata

Japanese journal of clinical oncology 51 ( 3 ) 434 - 443 2021.3

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The Japan Clinical Oncology Group 1505 trial is a single-arm multicentre prospective study that examined the possibility of non-surgical follow-up with endocrine therapy for patients with low-grade ductal carcinoma in situ. In that study, the eligible criteria included histopathological findings comprising low to intermediate nuclear grade and absence of comedo necrosis, and cases were entered according to the local histopathological diagnosis. Nuclear grade is largely based on the Consensus Conference criteria (1997), whereas comedo necrosis is judged according to the Rosen's criteria (2017). The purpose of this study was to standardize and examine the interobserver agreement levels of these histopathological criteria amongst the participating pathologists. METHODS: We held slide conferences, where photomicrographs of haematoxylin-eosin-stained slides from 68 patients with ductal carcinoma in situ were presented using PowerPoint. The nuclear grade and comedo necrosis statuses individually judged by the pathologists were analysed using κ statistics. RESULTS: In the first and second sessions, where 22 cases each were presented, the interobserver agreement levels of nuclear grade whether low/intermediate grade or high grade were moderate amongst 29 and 24 participating pathologists, respectively (κ = 0.595 and 0.519, respectively). In the third session where 24 cases were presented, interobserver agreement levels of comedo necrosis or non-comedo necrosis were substantial amongst 25 participating pathologists (κ = 0.753). CONCLUSION: Although the concordance rates in nuclear grade or comedo necrosis were not high in a few of the cases, we believe that these results could provide a rationale for employing the present criteria of nuclear grade and comedo necrosis in the clinical study of ductal carcinoma in situ.

DOI： 10.1093/jjco/hyaa235

Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women.

Kengo Kawada, Naruto Taira, Taeko Mizoo, Yoko Suzuki, Yukiko Kajiwara, Minami Hatono, Takahiro Tsukioki, Mariko Kochi, Yuko Abe, Keiko Nishiyama, Takayuki Iwamoto, Hirokuni Ikeda, Tadahiko Shien, Hiroyoshi Doihara, Setsuko Ishihara, Hiroshi Kawai, Kensuke Kawasaki, Yoichi Ishibe, Yutaka Ogasawara, Shinichi Toyooka

Breast cancer (Tokyo, Japan) 28 ( 2 ) 478 - 487 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

BACKGROUND: Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. METHODS: In previous case-control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. RESULTS: There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). CONCLUSIONS: SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

DOI： 10.1007/s12282-020-01185-x

Estimation of willingness-to-pay for breast cancer treatments through contingent valuation method in Japanese breast cancer patients (JCOG1709A); preliminary study findings

Tsuguo Iwatani, Fumikata Hara, Tadahiko Shien, Masato Takahashi, Norikazu Masuda, Hiroyuki Yasojima, Yasuaki Sagara, Tomonori Mizutani, Keita Sasaki, Kenichi Nakamura, Haruhiko Fukuda, Takaru Shiroiwa, Hiroji Iwata

CANCER RESEARCH 81 ( 4 ) 2021.2

Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments. International journal

Minami Hatono, Hirokuni Ikeda, Yoko Suzuki, Yukiko Kajiwara, Kengo Kawada, Takahiro Tsukioki, Mariko Kochi, Ken Suzawa, Takayuki Iwamoto, Hiromasa Yamamoto, Tadahiko Shien, Masaomi Yamane, Naruto Taira, Hiroyoshi Doihara, Shinichi Toyooka

Breast cancer research and treatment 185 ( 2 ) 307 - 316 2021.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

PURPOSE: Epidemiological studies have suggested that intake of soy isoflavones is associated with a reduced risk of development of breast cancer and an improved prognosis in patients with breast cancer. In addition, basic research has demonstrated the antitumor effects of these compounds on breast cancer cell lines. However, the detailed effects of the intake of equol, which is one of the metabolites of the soy isoflavones, are yet to be clarified on the risk of development and recurrence of breast cancer and its interactions with drugs used for treating breast cancer. This study aimed to determine the antitumor effects of equol and investigate the impact of adding equol to therapeutic agents for breast cancer using breast cancer cell lines. METHODS: We examined the antitumor effect of equol on breast cancer cell lines using MTS assay. We also studied the combined effect of equol and the existing hormonal or chemotherapeutic agents using combination index. We evaluated the expressions of the related proteins by Western blot analysis and correlated the findings with the antitumor effect. RESULTS: Equol showed bi-phasic protumor and antitumor effects; at a low concentration, it promoted the tumor growth in hormone receptor-positive cell lines, whereas antitumor effects were generally observed when an excessive amount of dose unexpected in the blood and the tissue was administered. When used with tamoxifen, equol might have some antagonistic effect, although it depends on equol concentration and the type of cancer cells. CONCLUSIONS: We confirmed that equol has dual action, specifically a tumor growth-promoting effect and an antitumor effect. Although the results suggested that equol might exert an antagonistic effect against tamoxifen depending on the concentration, equol did not exert an antagonistic effect on other therapeutic agents.

DOI： 10.1007/s10549-020-05957-z

Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma.

Takahiro Tsukioki, Tadahiko Shien, Yusuke Ohtani, Miwa Fujihara, Yoko Suzuki, Yukiko Kajihara, Minami Hatono, Kengo Kawada, Mariko Kochi, Takayuki Iwamoto, Hirokuni Ikeda, Naruto Taira, Hiroyoshi Doihara

Acta medica Okayama 74 ( 5 ) 401 - 406 2020.10

Language：English Publishing type：Research paper (scientific journal)

Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC.

DOI： 10.18926/AMO/60799

原発性乳癌に対する術前化学放射線療法の病理学的効果判定法の検討(JCOG0306A1)

枝園忠彦, 津田均, 佐々木啓太, 水澤純基, 秋山太, 黒住昌史, 澤木正孝, 田村宜子, 田中希世, 古川孝広, 高橋三奈, 林直輝, 向井博文, 増田慎三, 岩田広治

日本癌治療学会学術集会抄録集 58回 O51 - 4 2020.10

The efficacy of sequential second-line endocrine therapies (ETs) in postmenopausal estrogen receptor-positive and HER2-negative metastatic breast cancer patients with lower sensitivity to initial ETs. Reviewed

Takayuki Iwamoto, Tomomi Fujisawa, Tadahiko Shien, Kazuhiro Araki, Kentaro Sakamaki, Takafumi Sangai, Yuichiro Kikawa, Shintaro Takao, Reiki Nishimura, Masato Takahashi, Tomohiko Aihara, Hirofumi Mukai, Naruto Taira

Breast cancer (Tokyo, Japan) 27 ( 5 ) 973 - 981 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

PURPOSE: Second-line endocrine therapy (ET) for estrogen receptor (ER)-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) is offered based on the response to first-line ET. However, no clinical trials have evaluated the efficacy and safety of secondary ETs in patients with poor responses to initial ET. This study evaluated the efficacy of second-line ET in ER-positive and HER2-negative postmenopausal MBC patients with low or very low sensitivity to initial ET. METHODS: This multicenter prospective observational cohort study evaluated the response of 49 patients to second-line ETs in postmenopausal MBC patients with low or very low sensitivity to initial ET. The primary endpoint was the clinical benefit rate (CBR) for 24 weeks. RESULTS: Of the 49 patients assessed, 40 (82%) received fulvestrant in the second line, 5 (10%) received selective estrogen receptor modulators, 3 (6%) received aromatase inhibitors (AIs) alone, and 1 received everolimus with a steroidal AI. The overall CBR was 44.9% [90% confidence interval (CI): 34.6-57.6, p = 0.009]; CBR demonstrated similar significance across the progesterone receptor-positive (n = 39, 51.3%, 90% CI: 39.6-65.2, p = 0.002), very low sensitivity (n = 17, 58.8%, 90% CI: 42.0-78.8, p = 0.003), and non-visceral metastases (n = 25, 48.0%, 90% CI: 34.1-65.9, p = 0.018) groups. The median progression-free survival was 7.1 months (95% CI: 5.6-10.6). CONCLUSION: Second-line ET might be a viable treatment option for postmenopausal patients with MBC with low and very low sensitivity to initial ET. Future studies based on larger and independent cohorts are needed to validate these findings.

DOI： 10.1007/s12282-020-01095-y

Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer. Reviewed International journal

Kosuke Ochi, Ken Suzawa, Shuta Tomida, Kazuhiko Shien, Jui Takano, Shunsaku Miyauchi, Tatsuaki Takeda, Akihiro Miura, Kota Araki, Kentaro Nakata, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Tadahiko Shien, Masaomi Yamane, Kazuo Azuma, Yoshiharu Okamoto, Shinichi Toyooka

Biochemical and biophysical research communications 529 ( 3 ) 760 - 765 2020.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors. MATERIALS AND METHODS: A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed. RESULTS: TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor. CONCLUSION: Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance.

DOI： 10.1016/j.bbrc.2020.06.077