Predictive pharmacogenetic biomarkers for breast cancer recurrence prevention by simvastatin

Ahern, Thomas P.; Damkier, Per; Feddersen, Søren; Kjærsgaard, Anders; Lash, Timothy L.; Hamilton-Dutoit, Stephen; Lythjohan, Cathrine Bredal; Ejlertsen, Bent; Christiansen, Peer; Cronin-Fenton, Deirdre

doi:10.1080/0284186x.2020.1759820

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…Additionally, in patients recieving AZA, SLCO1B1 rs4149056 minor allele was protective against pulmonary fibrosis (p = 0.04), however this signal was completely lost after adjusting for confunding factors (p adj = 0.12). Even though alterantive allele protectiveness might be explained by longer drug exposure and similar results were present in several studies [46,47], those studies were focusing on different diseases and outcomes. Other study did not associate slow OATP1B1 transporters, or SLCO1B1 variant carriers, with reduced risk for kidney and heart failure in Diabetic Kidney Diseases patients [48].…”

Section: Discussionsupporting

confidence: 56%

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Jelovac,

Kotur,

Ristivojevic

et al. 2023

IJMS

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Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 were tested for association with severe disease outcomes in 102 patients with SSc from Serbia treated either with immunosuppressants azathioprine (AZA) and methotrexate (MTX) or with other types of medications. Genotyping was performed using PCR-RFLP and direct Sanger sequencing. R software was used for statistical analysis and development of polygenic risk score (PRS) model. Association was found between MTHFR rs1801133 and higher risk for elevated systolic pressure in all patients except those prescribed with MTX, and higher risk for kidney insufficiency in patients prescribed with other types of drugs. In patients treated with MTX, variant SLCO1B1 rs4149056 was protective against kidney insufficiency. For patients receiving MTX a trend was shown for having a higher PRS rank and elevated systolic pressure. Our results open a door wide for more extensive research on pharmacogenomics markers in patients with SSc. Altogether, pharmacogenomics markers could predict the outcome of patients with SSc and help in prevention of adverse drug reactions.

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Section: Discussionsupporting

confidence: 56%

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Jelovac,

Kotur,

Ristivojevic

et al. 2023

IJMS

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“…Furthermore, when combined with doxorubicin, simvastatin exhibited a synergic cytotoxic effect on CMC cells ( 280 ). However, despite good in vitro results, discouraging large meta-analyses have found no significant benefit from the use of simvastatin in patients suffering from HBC ( 281 – 283 ).…”

Section: Adjuvant Targeted Therapiesmentioning

confidence: 99%

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

et al. 2021

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Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. Canine mammary cancer (CMC) represents 50% of CMTs, and besides surgery, which is the elective treatment, additional targeted and non-targeted therapies could offer benefits in terms of survival to these patients. Also, CMC is considered a good spontaneous intermediate animal model for the research of human breast cancer (HBC), and therefore, the study of new treatments for CMC is a promising field in comparative oncology. Dogs with CMC have a comparable disease, an intact immune system, and a much shorter life span, which allows the achievement of results in a relatively short time. Besides conventional chemotherapy, innovative therapies have a large niche of opportunities. In this article, a comprehensive review of the current research in adjuvant therapies for CMC is conducted to gather available information and evaluate the perspectives. Firstly, updates are provided on the clinical–pathological approach and the use of conventional therapies, to delve later into precision therapies against therapeutic targets such as hormone receptors, tyrosine kinase receptors, p53 tumor suppressor gene, cyclooxygenases, the signaling pathways involved in epithelial–mesenchymal transition, and immunotherapy in different approaches. A comparison of the different investigations on targeted therapies in HBC is also carried out. In the last years, the increasing number of basic research studies of new promising therapeutic agents on CMC cell lines and CMC mouse xenografts is outstanding. As the main conclusion of this review, the lack of effort to bring the in vitro studies into the field of applied clinical research emerges. There is a great need for well-planned large prospective randomized clinical trials in dogs with CMC to obtain valid results for both species, humans and dogs, on the use of new therapies. Following the One Health concept, human and veterinary oncology will have to join forces to take advantage of both the economic and technological resources that are invested in HBC research, together with the innumerable advantages of dogs with CMC as a spontaneous animal model.

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“…Colorectal cancer is one of the most common malignant tumors worldwide, with the incidence ranking third among all malignant tumors, and the mortality ranking second [ 1 , 2 ]. The WHO Cancer Research Centre's GLOBOCAN project estimated that the number of new colorectal cancer cases worldwide in 2018 was approximately 1.8 million and the number of deaths was approximately 880,000 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Simvastatin in the Treatment of Colorectal Cancer: A Review

Zang

Yang

Tian

2022

Evidence-Based Complementary and Alternative Medicine

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Drug repositioning and drug reuse are the heated topics in the field of oncology in recent years. These two concepts refer to seeking effective drugs for cancer that are not originally intended to treat cancer. The survival benefits are then analyzed by combining the re-positioned drugs with conventional cancer treatment methods. Simvastatin is a clinically commonly used hyperlipidemia drug and exerts the effect of preventing cardiovascular diseases. Recent studies have found that simvastatin has great potential in the treatment of colorectal cancer, and a large number of clinical studies have used simvastatin as an adjuvant drug to help treat metastatic colorectal cancer.

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Predictive pharmacogenetic biomarkers for breast cancer recurrence prevention by simvastatin

Abstract: Per Damkier (2),(3) , Søren Feddersen (2),(3) , Anders Kjaersgaard (4) , Timothy L. Lash (5) , Stephen Hamilton-Dutoit (6) , Cathrine Bredal Lythjohan (6) , Bent Ejlertsen (7),(8) , Peer M. Christiansen (7),( 9) , Deirdre P. Cronin-Fenton (4)

Cited by 5 publications

References 32 publications

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

Simvastatin in the Treatment of Colorectal Cancer: A Review

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