Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer: Youngjoo Lee, Soo-Hyun Lee, Geon Kook Lee, Eun Jin Lim, Ji-Youn Han; Cancer Res Treat. 2023;55(3):885-893. Published online March 20, 2023; DOI: https://doi.org/10.4143/crt.2023.283

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Purpose
This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC).
Materials and Methods
This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate.
Results
Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046).
Conclusion
Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

Citations

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Cardiovascular/anti‐inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta‐analysis of randomized trials
David J. Benjamin, Alyson Haslam, Vinay Prasad
Cancer Medicine.2024;[Epub] CrossRef
Repurposing simvastatin in cancer treatment: an updated review on pharmacological and nanotechnological aspects
Nargis Ara, Abdul Hafeez, Shom Prakash Kushwaha
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(10): 7377. CrossRef
Strategies to Target Chemoradiotherapy Resistance in Small Cell Lung Cancer
Tony Yu, Benjamin H. Lok
Cancers.2024; 16(20): 3438. CrossRef
β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers
Pedro Gabriel Senger Braga, Janaína da Silva Vieira, Aline Rachel Bezerra Gurgel, Patricia Chakur Brum
Frontiers in Pharmacology.2024;[Epub] CrossRef
Statins—From Fungi to Pharmacy
Anna Sadowska, Patryk Osiński, Alicja Roztocka, Karolina Kaczmarz-Chojnacka, Ewa Zapora, Diana Sawicka, Halina Car
International Journal of Molecular Sciences.2023; 25(1): 466. CrossRef

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Gastrointestinal cancer

A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer: Hyunji Jo, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Jeong Il Yu, Hee Chul Park, Doo Ho Choi, Yoonah Park, Yong Beom Cho, Jung Wook Huh, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Won Ki Kang; Cancer Res Treat. 2023;55(1):189-195. Published online June 8, 2022; DOI: https://doi.org/10.4143/crt.2021.1527

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Purpose
The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC).
Materials and Methods
Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity.
Results
Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin.
Conclusion
The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

Citations

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Short- and long-term outcomes of neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy for locally advanced rectal cancer: an updated meta-analysis
Yue Guo, Zhifeng Guo, Jiaojiao Zhang, Guowu Qian, Wangquan Ji, Linlin Song, Zhe Guo, Zhuo Han
BMC Gastroenterology.2025;[Epub] CrossRef
A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
Prachi S. Patil, Avanish Saklani, Naveena A. N. Kumar, Ashwin De’Souza, Rahul Krishnatry, Snehal Khanvilkar, Mufaddal Kazi, Reena Engineer, Vikas Ostwal, Anant Ramaswamy, Munita Bal, Priya Ranganathan, Ekta Gupta, Sanjeev Galande
Frontiers in Oncology.2025;[Epub] CrossRef
Effects of Hyperlipidemia on Osseointegration of Dental Implants and Its Strategies
Haiyang Sun, Shuhuai Meng, Junyu Chen, Qianbing Wan
Journal of Functional Biomaterials.2023; 14(4): 194. CrossRef

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Breast Cancer

Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: Erwin Danil Yulian, Nurjati Chairani Siregar, Bajuadji; Cancer Res Treat. 2021;53(4):1072-1083. Published online March 9, 2021; DOI: https://doi.org/10.4143/crt.2020.1024

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Purpose
The efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Preclinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with fluorouracil, adriamycin, and cyclophosphamide (FAC) therapy in LABC patients.
Materials and Methods
We undertook a randomized, double-blinded, placebo-controlled trial in two centers of Indonesia. Patients were randomly assigned to FAC plus simvastatin (40 mg/day orally) or FAC plus placebo (40 mg/day) for 21 days. The FAC regimen was repeated every 3 weeks. We evaluated the clinical response, pathological response, and toxicities.
Results
The objective response rate (ORR) for FAC plus simvastatin was 90% (95% confidence interval [CI], 0.99 to 1.67) by per-protocol analysis. No complete responses (CR) were recorded, but there were 48 partial responses. No significant difference was observed between the two groups with the ORR (p=0.103). The pathological CR rate was 6.25% (2 in simvastatin group and 1 in placebo group). Adverse events in both arms were generally mild, mainly consisted of myotoxicity. Human epidermal growth factor receptor 2 (HER2) expression was a factor related to the success of therapeutic response (odds ratio, 4.2; 95% CI, 1.121 to 15.731; p=0.033).
Conclusion
This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC. Although no statistically significant difference was documented, there was a trend for better activity and tolerability. The addition of 40 mg simvastatin may improve the efficacy of FAC in LABC patients with HER2 overexpression.

Citations

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Theoretical framework and emerging challenges of lipid metabolism in cancer
Qiuying Gu, Yuan Wang, Ping Yi, Chunming Cheng
Seminars in Cancer Biology.2025; 108: 48. CrossRef
Clinical significance of lipid pathway-targeted therapy in breast cancer
Dan Li, Pengcheng Jin, Yiqi Cai, Shijie Wu, Xianan Guo, Zhiyun Zhang, Kexin Liu, Panni Li, Yue Hu, Yunxiang Zhou
Frontiers in Pharmacology.2025;[Epub] CrossRef
Anticancer properties of histone deacetylase inhibitors – what is their potential?
Kajetan Kiełbowski, Agata Szwedkowicz, Paulina Plewa, Estera Bakinowska, Rafał Becht, Andrzej Pawlik
Expert Review of Anticancer Therapy.2025; 25(2): 105. CrossRef
Divide and Conquer—Targeted Therapy for Triple-Negative Breast Cancer
Milica Nedeljković, Ana Vuletić, Katarina Mirjačić Martinović
International Journal of Molecular Sciences.2025; 26(4): 1396. CrossRef
Factors Affecting Pathological Complete Response in Locally Advanced Breast Cancer Cases Receiving Neoadjuvant Therapy: A Comprehensive Literature Review
Munaser Alamoodi
European Journal of Breast Health.2024; 20(1): 8. CrossRef
Role of hydroxymethylglutharyl-coenzyme A reductase in the induction of stem-like states in breast cancer
María Paula Marks, Carla Alejandra Giménez, Luciana Isaja, Mariana Belén Vera, Francisco Raúl Borzone, Federico Pereyra-Bonnet, Leonardo Romorini, Guillermo Agustín Videla-Richardson, Norma Alejandra Chasseing, Juan Carlos Calvo, Luciano Vellón
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Cardiovascular/anti‐inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta‐analysis of randomized trials
David J. Benjamin, Alyson Haslam, Vinay Prasad
Cancer Medicine.2024;[Epub] CrossRef
Are statins onco- suppressive agents for every type of tumor? A systematic review of literature
Luca Filaferro, Fabiana Zaccarelli, Giovanni Francesco Niccolini, Andrea Colizza, Federica Zoccali, Michele Grasso, Massimo Fusconi
Expert Review of Anticancer Therapy.2024; 24(6): 435. CrossRef
Post-surgery statin use contributes to favorable outcomes in patients with early breast cancer
María Belén Giorello, María Paula Marks, Tiago Martín Osinalde, María del Rosario Padin, Alejandra Wernicke, Juan Carlos Calvo, Norma Alejandra Chasseing, Luciano Vellón
Cancer Epidemiology.2024; 90: 102573. CrossRef
Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways
Fahad Khan, Deena Elsori, Meenakshi Verma, Shivam Pandey, Safia Obaidur Rab, Samra Siddiqui, Nadiyah M. Alabdallah, Mohd Saeed, Pratibha Pandey
Frontiers in Cell and Developmental Biology.2024;[Epub] CrossRef
Obesity-Associated Colorectal Cancer
Lucia Gonzalez-Gutierrez, Omar Motiño, Daniel Barriuso, Juan de la Puente-Aldea, Lucia Alvarez-Frutos, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
International Journal of Molecular Sciences.2024; 25(16): 8836. CrossRef
Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer
Lei Li, Hongbin Wang, Shiyuan Zhang, Song Gao, Xiuxin Lu, You Pan, Wei Tang, Rong Huang, Kun Qiao, Shipeng Ning
International Journal of Surgery.2024; 110(8): 4716. CrossRef
Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target
Molly E. Muehlebach, Sarah A. Holstein
Clinical and Translational Medicine.2023;[Epub] CrossRef
The role of HMGCR expression in combination therapy of simvastatin and FAC treated locally advanced breast cancer patients
Erwin Danil Yulian, Nurjati Chairani Siregar, Bajuadji Sudijono, Lie Rebecca Yen Hwei
Breast Disease.2023; 42(1): 73. CrossRef
A phase 1 study of simvastatin in combination with topotecan and cyclophosphamide in pediatric patients with relapsed and/or refractory solid and CNS tumors
Thomas Cash, Hunter C. Jonus, Maya Tsvetkova, Jan H. Beumer, Arhanti Sadanand, Jasmine Y. Lee, Curtis J. Henry, Dolly Aguilera, R. Donald Harvey, Kelly C. Goldsmith
Pediatric Blood & Cancer.2023;[Epub] CrossRef
New insights into the therapeutic potentials of statins in cancer
Chengyu Liu, Hong Chen, Bicheng Hu, Jiajian Shi, Yuchen Chen, Kun Huang
Frontiers in Pharmacology.2023;[Epub] CrossRef
Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics
Hao-Ran Jin, Jin Wang, Zi-Jing Wang, Ming-Jia Xi, Bi-Han Xia, Kai Deng, Jin-Lin Yang
Journal of Hematology & Oncology.2023;[Epub] CrossRef
Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance
Zsuzsanna Schelz, Hiba F. Muddather, István Zupkó
Antibiotics.2023; 12(9): 1468. CrossRef
Dysregulation of cholesterol metabolism in cancer progression
Xuesong Liu, Mengzhu Lv, Weimin Zhang, Qimin Zhan
Oncogene.2023; 42(45): 3289. CrossRef
p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells
Giorgia Centonze, Dora Natalini, Silvia Grasso, Alessandro Morellato, Vincenzo Salemme, Alessio Piccolantonio, Giacomo D’Attanasio, Aurora Savino, Olga Teresa Bianciotto, Matteo Fragomeni, Andrea Scavuzzo, Matteo Poncina, Francesca Nigrelli, Mario De Greg
Cell Death & Disease.2023;[Epub] CrossRef
Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer
Yoichi Morofuji, Shinsuke Nakagawa, Kenta Ujifuku, Takashi Fujimoto, Kaishi Otsuka, Masami Niwa, Keisuke Tsutsumi
Pharmaceuticals.2022; 15(2): 151. CrossRef
Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis
Ahmed Sayed, Omar M. Abdelfattah, Malak Munir, Omar Shazly, Ahmed K. Awad, Hazem S. Ghaith, Khaled Moustafa, Maria Gerew, Avirup Guha, Ana Barac, Michael G. Fradley, George S. Abela, Daniel Addison
European Journal of Cancer.2022; 169: 82. CrossRef
Simvastatin in the Treatment of Colorectal Cancer: A Review
Hongliang Zang, Wei Yang, Xiaofeng Tian, Tian Jiao Wang
Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1. CrossRef
Mutant p53, the Mevalonate Pathway and the Tumor Microenvironment Regulate Tumor Response to Statin Therapy
Madison Pereira, Kathy Matuszewska, Alice Glogova, Jim Petrik
Cancers.2022; 14(14): 3500. CrossRef
Repurposing of metabolic drugs and mitochondrial modulators as an emerging class of cancer therapeutics with a special focus on breast cancer
Versha Tripathi, Pooja Jaiswal, Khageswar Sahu, Shovan Kumar Majumder, Dharmendra Kashyap, Hem Chandra Jha, Amit Kumar Dixit, Hamendra Singh Parmar
Advances in Cancer Biology - Metastasis.2022; 6: 100065. CrossRef
Repurposing of Metabolic Drugs and Mitochondrial Modulators as an Emerging Class of Cancer Therapeutics with a Special Focus on Breast Cancer
Hamendra Singh Singh Parmar, Versha Tripathi, Pooja Jaiswal, Khageshwar Sahu, Shovan Kumar Majumder, Dharmendra Kashyap, Amit Kumar Dixit, Hem Chandra Jha
SSRN Electronic Journal .2022;[Epub] CrossRef
Statins: a repurposed drug to fight cancer
Wen Jiang, Jin-Wei Hu, Xu-Ran He, Wei-Lin Jin, Xin-Yang He
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef

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Breast cancer

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients: Mihong Choi, Jiyeon Han, Bo Ram Yang, Myoung-jin Jang, Miso Kim, Dae-Won Lee, Tae-Yong Kim, Seock-Ah Im, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee; Cancer Res Treat. 2021;53(1):65-76. Published online September 23, 2020; DOI: https://doi.org/10.4143/crt.2020.430

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
Materials and Methods
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Results
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Conclusion
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

Citations

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Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics
Santosh Kumar Maurya, Smriti Chaudhri, Shashank Kumar, Sanjay Gupta
Pharmaceutical Research.2025; 42(1): 49. CrossRef
Are statins onco- suppressive agents for every type of tumor? A systematic review of literature
Luca Filaferro, Fabiana Zaccarelli, Giovanni Francesco Niccolini, Andrea Colizza, Federica Zoccali, Michele Grasso, Massimo Fusconi
Expert Review of Anticancer Therapy.2024; 24(6): 435. CrossRef
Investigating the relationship between insulin use and all-cause mortality, breast cancer mortality, and recurrence risk in diabetic patients with breast cancer: A comprehensive systematic review and meta-analysis
Marina V. Loktionova, Mahdi Mohammadian, Roya Choopani, Soleiman Kheiri, Abdollah Mohammadian-Hafshejani, Kathleen Bennett
PLOS ONE.2024; 19(12): e0314565. CrossRef
Impact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis
Xiaolin Jia, Ye Lu, Zili Xu, Qingqing Mu
Frontiers in Oncology.2023;[Epub] CrossRef
Effect of statins use on risk and prognosis of breast cancer: a meta-analysis
Guodong Zhao, Yanjun Ji, Qing Ye, Xin Ye, Guanqun Wo, Xi Chen, Xinyi Shao, Jinhai Tang
Anti-Cancer Drugs.2022; 33(1): e507. CrossRef
Studying the Cytotoxic Activity of Newly Designed and Synthesized HDAC Inhibitors Derivatives of Pentanoyl Anilide‐5‐Biguanide
Othman Makki Sagheer, Mohammed Hassan Mohammed, Jaafar S. Wadi, Zaid O. Ibraheem
Macromolecular Symposia.2022;[Epub] CrossRef
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Mónica Cejuela, Begoña Martin-Castillo, Javier A. Menendez, Sonia Pernas
International Journal of Molecular Sciences.2022; 23(5): 2705. CrossRef
Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression
Giorgia Centonze, Dora Natalini, Alessio Piccolantonio, Vincenzo Salemme, Alessandro Morellato, Pietro Arina, Chiara Riganti, Paola Defilippi
Frontiers in Oncology.2022;[Epub] CrossRef
Synthesis of gamma biguanides butyric acid analogues as HDAC inhibitors and studying their cytotoxic activity
Othman Makki Sagheer, Mohammed Hassan Mohammed, Zaid O. Ibraheem, Jaafar S. Wadi, Mustafa F. Tawfeeq
Materials Today: Proceedings.2021; 47: 5983. CrossRef
Statins: a repurposed drug to fight cancer
Wen Jiang, Jin-Wei Hu, Xu-Ran He, Wei-Lin Jin, Xin-Yang He
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef
Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study
Byoung Hyuck Kim, Moon-June Cho, Jeanny Kwon
International Journal of Clinical Oncology.2021; 26(11): 2004. CrossRef

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A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients: Youjin Kim, Tae Won Kim, Sae Won Han, Joong Bae Ahn, Seung Tae Kim, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2019;51(3):1128-1134. Published online November 21, 2018; DOI: https://doi.org/10.4143/crt.2018.379

Abstract PDF PubReader ePub

Purpose
Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).
Materials and Methods
Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity.
Results
From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation.
Conclusion
Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.

Citations

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Anticancer properties of histone deacetylase inhibitors – what is their potential?
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Therapeutic Effects of Statins: Promising Drug for Topical and Transdermal Administration
Fatemeh Zahedipour, Seyede Atefe Hosseini, Željko Reiner, Eugenia Tedeschi-Reiner, Tannaz Jamialahmadi, Amirhossein Sahebkar
Current Medicinal Chemistry.2024; 31(21): 3149. CrossRef
Are statins onco- suppressive agents for every type of tumor? A systematic review of literature
Luca Filaferro, Fabiana Zaccarelli, Giovanni Francesco Niccolini, Andrea Colizza, Federica Zoccali, Michele Grasso, Massimo Fusconi
Expert Review of Anticancer Therapy.2024; 24(6): 435. CrossRef
Cholesterol synthesis is essential for the growth of liver metastasis‐prone colorectal cancer cells
Kumiko Taniguchi, Kei Sugihara, Takashi Miura, Daisuke Hoshi, Susumu Kohno, Chiaki Takahashi, Eishu Hirata, Etsuko Kiyokawa
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A phase 1 study of simvastatin in combination with topotecan and cyclophosphamide in pediatric patients with relapsed and/or refractory solid and CNS tumors
Thomas Cash, Hunter C. Jonus, Maya Tsvetkova, Jan H. Beumer, Arhanti Sadanand, Jasmine Y. Lee, Curtis J. Henry, Dolly Aguilera, R. Donald Harvey, Kelly C. Goldsmith
Pediatric Blood & Cancer.2023;[Epub] CrossRef
New insights into the therapeutic potentials of statins in cancer
Chengyu Liu, Hong Chen, Bicheng Hu, Jiajian Shi, Yuchen Chen, Kun Huang
Frontiers in Pharmacology.2023;[Epub] CrossRef
The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study
Sami Erkinantti, Ari Hautakoski, Reijo Sund, Martti Arffman, Elina Urpilainen, Ulla Puistola, Arja Jukkola, Karihtala Peeter, Esa Läärä
Cancer Control.2022;[Epub] CrossRef
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Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis
Navneet Kumar, Chandi C. Mandal
Frontiers in Genetics.2021;[Epub] CrossRef
Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance
Shangwei Zhong, Changhao Huang, Zhikang Chen, Zihua Chen, Jun-Li Luo
Journal of Clinical Medicine.2021; 10(21): 5000. CrossRef
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Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer: Youngjoo Lee, Ki Hyeong Lee, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Yun Jung Go, Jin Soo Lee, Ji-Youn Han; Cancer Res Treat. 2017;49(4):1001-1011. Published online January 13, 2017; DOI: https://doi.org/10.4143/crt.2016.546

Abstract PDF PubReader ePub

Purpose
This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).
Materials and Methods
Patientswith advancedNA-NSCLCwho progressed after one ortwo chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).
Results
Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).
Conclusion
There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.

Citations

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Research progress on cholesterol metabolism and tumor therapy
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Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin: Young-Suk Kim, Chang-Hwan Seol, Jae-Wan Jung, Su-Jin Oh, Ki-Eun Hwang, Hwi-Jung Kim, Eun-Taik Jeong, Hak-Ryul Kim; Cancer Res Treat. 2015;47(1):90-100. Published online October 27, 2014; DOI: https://doi.org/10.4143/crt.2013.194

Abstract PDF PubReader ePub

Purpose
Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells.
Materials and Methods
Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin.
Results
Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis.
Conclusion
Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.

Citations

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Sulindac exhibits anti-proliferative and anti-invasive effects and enhances the sensitivity to paclitaxel in ovarian cancer
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Regulatory effects of statins on Akt signaling for prevention of cancers
Fatemeh Sadat Hosseini, Abdolreza Ahmadi, Prashant Kesharwani, Hossein Hosseini, Amirhossein Sahebkar
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Sulindac exhibits anti-proliferative and anti-invasive effects in uterine serous carcinoma cells
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Celecoxib and sulindac inhibit TGF-β1-induced epithelial-mesenchymal transition and suppress lung cancer migration and invasion via downregulation of sirtuin 1
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Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors: Hee Sung Kim, Hye Seung Lee, Woo Ho Kim; Cancer Res Treat. 2011;43(3):181-188. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.181

Abstract PDF PubReader ePub

PURPOSE
This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
MATERIALS AND METHODS
Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5.
RESULTS
COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001).
CONCLUSION
Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.

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A Histone Deacetylase Inhibitor, Trichostatin A, Enhances Radiosensitivity by Abrogating G2/M Arrest in Human Carcinoma Cells: In Ah Kim, Jin Ho Kim, Jin Hee Shin, Il Han Kim, Jae Sung Kim, Hong-Gyun Wu, Eui Kyu Chie, Yong Ho Kim, Bo-Kyung Kim, Semie Hong, Seok Won Park, Sung Whan Ha, Charn Il Park; Cancer Res Treat. 2005;37(2):122-128. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.122

Abstract PDF PubReader ePub

Purpose

Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction.

Materials and Methods

A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed.

Results

TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner.

Conclusion

The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiation-induced G2/M arrest.

Citations

Citations to this article as recorded by

Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Radiosensitizing effect of dendrosomal nanoformulation of curcumin on cancer cells
Tahereh Jalali Varnamkhasti, Meisam Jafarzadeh, Majid Sadeghizadeh, Mahdi Aghili
Pharmacological Reports.2022; 74(4): 718. CrossRef
Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review
Abdelhakim Bouyahya, Nasreddine El Omari, Mohamed Bakha, Tarik Aanniz, Naoual El Menyiy, Naoufal El Hachlafi, Aicha El Baaboua, Mohamed El-Shazly, Mohammed Merae Alshahrani, Ahmed Abdullah Al Awadh, Learn-Han Lee, Taoufiq Benali, Mohammad S. Mubarak
Pharmaceuticals.2022; 15(10): 1235. CrossRef
Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells
Fengqiu Zhang, Changsheng Shao, Zhu Chen, Yalin Li, Xumiao Jing, Qing Huang
Radiation Research.2021;[Epub] CrossRef
Targeted Therapeutic Strategies for Triple-Negative Breast Cancer
Ying Li, Zhijun Zhan, Xuemin Yin, Shujun Fu, Xiyun Deng
Frontiers in Oncology.2021;[Epub] CrossRef
Is level of acetylation directly correlated to radiation sensitivity of cancer cell?
Fengqiu Zhang, Zhu Chen, Changsheng Shao, Qing Huang
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.2019; 813: 13. CrossRef
Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53
Manuela Terranova-Barberio, Biagio Pecori, Maria Serena Roca, Serena Imbimbo, Francesca Bruzzese, Alessandra Leone, Paolo Muto, Paolo Delrio, Antonio Avallone, Alfredo Budillon, Elena Di Gennaro
Journal of Experimental & Clinical Cancer Research.2017;[Epub] CrossRef
Histone Acetylation Induced Transformation of B-DNA to Z-DNA in Cells Probed through FT-IR Spectroscopy
Fengqiu Zhang, Qing Huang, Jingwen Yan, Zhu Chen
Analytical Chemistry.2016; 88(8): 4179. CrossRef
Cell-based multi-substrate assay coupled to UHPLC-ESI-MS/MS for a quick identification of class-specific HDAC inhibitors
Vincent Zwick, Claudia Simões-Pires, Muriel Cuendet
Journal of Enzyme Inhibition and Medicinal Chemistry.2016; 31(sup1): 209. CrossRef
Assessment of the Effect of Trichostatin A on HeLa Cells through FT-IR Spectroscopy
Fengqiu Zhang, Qing Huang, Jingwen Yan, Xin Zhang, Jianxin Li
Analytical Chemistry.2015; 87(4): 2511. CrossRef
Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells
Ahrum Min, Seock-Ah Im, Debora Keunyoung Kim, Sang-Hyun Song, Hee-Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Mark J O’Connor, Yung-Jue Bang
Breast Cancer Research.2015;[Epub] CrossRef
CD44 is a biomarker associated with human prostate cancer radiation sensitivity
WeiWei Xiao, Peter H. Graham, Carl A. Power, Jingli Hao, John H. Kearsley, Yong Li
Clinical & Experimental Metastasis.2012; 29(1): 1. CrossRef
Identification of a radiosensitivity signature using integrative metaanalysis of published microarray data for NCI-60 cancer cells
Han Sang Kim, Sang Cheol Kim, Sun Jeong Kim, Chan Hee Park, Hei-Cheul Jeung, Yong Bae Kim, Joong Bae Ahn, Hyun Cheol Chung, Sun Young Rha
BMC Genomics.2012;[Epub] CrossRef
In vivoRadiosensitization Effect of HDAC Inhibitor, SK-7041 on RIF-1 Cell Line
Eui Kyu Chie, Jin Hee Shin, In Ah Kim, Il Han Kim
The Journal of the Korean Society for Therapeutic Radiology and Oncology.2010; 28(4): 219. CrossRef
Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: Potential role of histone deacetylase 6
In Ah Kim, Mina No, Jang Mi Lee, Jin Hee Shin, Jee Sun Oh, Eun Jung Choi, Il Han Kim, Peter Atadja, Eric J. Bernhard
Radiotherapy and Oncology.2009; 92(1): 125. CrossRef
Histone Deacetylase Inhibitor–Mediated Radiosensitization of Human Cancer Cells: Class Differences and the Potential Influence of p53
In Ah Kim, Jin Hee Shin, Il Han Kim, Jin Ho Kim, Jae Sung Kim, Hong Gyun Wu, Eui Kyu Chie, Sung Whan Ha, Charn Il Park, Gary D. Kao
Clinical Cancer Research.2006; 12(3): 940. CrossRef

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Suppression of Peritoneal Metastases by Expression of Murine Endostatin cDNA: Seung Ho Choi, Jae Hoon Lee, Sung Hee Hong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min; Cancer Res Treat. 2002;34(4):302-307. Published online August 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.4.302

Abstract PDF

Peritoneal seeding is one of problems to be solved in gastrointestinal and ovarian cancers. Angiogenesis is the critical step for a dormancy tumor cluster to be an overt metastatic nodule. However, whether an anti-angiogenesis strategy is effective in the control of peritoneal metastases is still obscure. In this study, we evaluated whether endostatin, an endogenous angiogenesis inhibitor, suppresses peritoneal metastases.
MATERIALS AND METHODS
We transduced a human gastric cancer cell line, AGS and a murine renal cancer cell line, Renca, with the plasmid pEndoSTHB, which encodes a secretable form of murine endostatin. Endostatin expression was tested with western blotting, and the biological activity of the secreted endostatin was confirmed with in vitro endothelial cell growth inhibition. In the animal experiments, stable transfectants were injected intraperitoneally.
RESULTS
We demonstrated secretion of endostatin from two cell lines transduced with the plasmid pEndoSTHB. Conditioned media secreted from pEndoSTSB-transduced mammalian cells were shown to potently inhibit endothelial cell growth in vitro. We selected stable transfectants with similar in vitro growth rates of their parental cell lines. Significant tumor growth inhibition was observed in the endostatin-expressing Renca cells intraperitoneal injection group at days of 28, compared to the null transfectants intraperitoneal injection control group.
CONCLUSION
These results support that peritoneal seeding is angiogenesis-dependant and an anti-angiogenesis strategy is a good way to control peritoneal metastases.

Citations

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The kringle domain of tissue-type plasminogen activator inhibits in vivo tumor growth
Byoung-Shik Shim, Byoung-Hak Kang, Yong-Kil Hong, Hyun-Kyung Kim, Il-Ha Lee, Soo-Young Lee, Young-Joon Lee, Suk-Keun Lee, Young Ae Joe
Biochemical and Biophysical Research Communications.2005; 327(4): 1155. CrossRef

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1 Crossref

cDNA Cloning and Expression of Angiostatin, an Angiogenesis Inhibitor , from Human Liver Tissue mRNA: Myung Jin Park, Byung Gap Hwang, Young Sook Son, Dong Hee Yi, Seong Hoon Lee, Seok II Hong; J Korean Cancer Assoc. 1999;31(6):1236-1245.

Abstract PDF: PURPOSE
Angiostatin, a 38 kDa internal fragment of plasminogen, is a potent inhibitor of angiogenesis. It blocks neovascularization and growth of primary and metastatic tumors in mice. To produce recombinant angiostatin protem comprising kringle 1-4 of plasminogen, we cloned the angiostatin cDNA from human liver tissue mRNA and expressed it in E. coli.
MATERIALS AND METHODS
We cloned angiostatin cDNA from human liver tissue mRNA using reverse transcriptase polymerase chain reaction (RT-PCR) method. Cloned cDNA was ligated to pET22b (+) expression vector, transformed into E. coli stram BL21 (DE3) and expressed by IPTG induction. Recombinant human angiostatin protein was purified from the inclusion bodies of lysated bacterial pellet with 8 M urea solubilization, refolding, single step Lysine-Sepharose 4B affinity chromatography and 0.2 M E-aminocarproic acid elution. The anti-angiogenic activity of purified recombinant angiostatin was assayed with endothelial cell proliferation assay and chorioallantoic membrane assay (CAM).
RESULTS
The identification of cloned angiostatin cDNA was confirmed by Southern hybridization and Pst I restriction enzyme digestion pattern. Angiostatin cDNA was expressed in E. coli, refolded in vitro and purified by Lysine Sepharose 4B affinity chromatography. The molecular weight of purified recombinant angiostatin was about 55 kDa on the SDS-PAGE. It inhibited the proliferation of bovine capillary endothelial (BCE) cells in vitro with a half-maximal inhibition concentration (ED50) of approximately 500 ng/mL. It also suppressed neovasculrization on the CAM assay.
CONCLUSION
These results demonstrated that recombinant human angiostatin has similar function and biological activity compared with human angiostatin which is purified from porcine elastase digested human plasminogen fragment.

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Effects of Lovastatin in Combination with 5-FU on Stomach Cancer Cells: Chaehwa Park, Won Ki Kang; J Korean Cancer Assoc. 1997;29(5):785-790.

Abstract PDF: No abstract available

2,576 View
15 Download

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