Effects of selumetinib: A Synthesis of Findings from 11 Studies

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Original Abstract of the Article

Major Research Findings

Selumetinib is a MEK 1/2 inhibitor currently in clinical trials for various solid malignancies. 8 found that selumetinib can cause dermatologic side effects, including skin, hair, and nail problems. 3 reported that selumetinib can cause peripheral edema and hair color changes in children treated for plexiform neurofibromas. 9 developed a new MEK inhibitor, NFX-179, for chemoprevention of squamous cell carcinoma. This topical agent was shown to be effective in a mouse model without any observed toxicities. 5 investigated the combined use of selumetinib and 5-FU for treating KRAS or BRAF mutant colon cancer and found that the sequence of administration is important, with better results seen when 5-FU is given first. 11 examined the effects of CKBA on mast cell activation in atopic dermatitis. It was shown that CKBA can suppress mast cell activation through the ERK signaling pathway. 2 explored the potential of using selumetinib in combination with thiostrepton to inhibit metastasis in triple-negative breast cancer. 7 1 studied the pharmacokinetics of selumetinib and found that its levels in the body can be affected by CYP3A4 and CYP2C19 inhibitors and inducers. 10 identified specific subtypes of adipocytes in the tumor-adipose microenvironment that can promote cancer progression.

Benefits and Risks

Benefit Summary

Selumetinib has shown promise in treating various cancers by inhibiting the growth of cancer cells. 8 3 9 5 11 2 7 1 10 Several studies suggest that selumetinib, either alone or in combination with other treatments, can slow down the progression of cancer. Additionally, it has potential for skin cancer prevention.

Risk Summary

Selumetinib use can lead to various side effects including skin problems, hair and nail abnormalities, peripheral edema, and changes in hair color. 8 3 9 5 11 2 7 1 10 Interactions with other medications can affect the levels of selumetinib in the body.

Comparison Between Studies

Commonalities

Many studies demonstrate the effectiveness of selumetinib as a MEK inhibitor, indicating its ability to inhibit cancer cell growth. Furthermore, its potential use for treating various cancers is highlighted across these studies.

Differences

Differences exist in terms of the extent of selumetinib's effectiveness, the severity of side effects, the type of cancers targeted, and the administration methods and accompanying medications. It is crucial to consider these variations when interpreting the findings.

Consistency and Contradictions in Results

While selumetinib has shown promise in inhibiting cancer cell growth in various studies, the degree of effectiveness and the severity of side effects can vary. The effectiveness of selumetinib might also depend on the type of cancer being treated and the method of administration. Further research is necessary to gain a comprehensive understanding of selumetinib's effects and side effects.

Implications for Everyday Life

Selumetinib holds potential for treating various cancers, but it's important to be aware of the associated risks. When using selumetinib, it's crucial to follow the doctor's instructions and monitor for any potential side effects.

Limitations of Current Research

The research on selumetinib is still incomplete. Further research is required, particularly regarding its long-term effects and side effects.

Future Research Directions

Future research should focus on understanding the long-term effects and side effects of selumetinib, investigating optimal administration methods, and assessing the efficacy of combination therapies. Identifying the specific cancer types and patients who would benefit most from selumetinib is also crucial.

Conclusion

Selumetinib holds promise as a MEK inhibitor with the potential to inhibit cancer cell growth. However, it's important to consider the associated risks. When using selumetinib, follow your doctor's instructions and be vigilant for any possible side effects. Additional research on selumetinib is necessary for a complete understanding of its potential benefits and risks.

Literature analysis of 11 papers
Positive Content
9
Neutral Content
0
Negative Content
2
Article Type
3
0
0
0
11
1.

Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects.

Author: TomkinsonHelen, McBrideEileen, MartinPaul, LisbonEleanor, DymondAngela W, CantariniMireille, SoKaren, HoltDavid

Selumetinib activity
Capsule manufacture change

Selumetinib, a potent inhibitor of mitogen-activated protein kinase 1/2, has shown promise in treating various cancers. This study evaluated the safety and efficacy of the Phase III formulation of selumetinib capsules in healthy subjects.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

Selumetinib side effects in children treated for plexiform neurofibromas: first case reports of peripheral edema and hair color change.

Author: BaldoFrancesco, MagnolatoAndrea, BarbiEgidio, BrunoIrene

Plexiform neurofibroma treatment
Dermatologic side effects
Gastrointestinal side effects
Lab abnormalities

Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, effectively tackles the growth of plexiform neurofibromas (PNs). The most common side effects are mild to moderate and include gastrointestinal symptoms, dermatologic manifestations, and laboratory test abnormalities.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Selumetinib in the Treatment of Symptomatic Intractable Plexiform Neurofibromas in Neurofibromatosis Type 1: A Prospective Case Series with Emphasis on Side Effects.

Author: BaldoFrancesco, GrassoAntonio Giacomo, Cortellazzo WielLuisa, MaestroAlessandra, TrojniakMarta Paulina, MurruFlora Maria, BassoLuca, MagnolatoAndrea, BrunoIrene, BarbiEgidio

Clinical response
PN treatment

Plexiform neurofibromas (PN) are tumors associated with neurofibromatosis type 1. This study reviewed the potential of selumetinib, a MEK inhibitor, in treating PN.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects.

Author: TomkinsonHelen, McBrideEileen, MartinPaul, LisbonEleanor, DymondAngela W, CantariniMireille, SoKaren, HoltDavid

Selumetinib activity
Capsule manufacture change

Selumetinib, a potent inhibitor of mitogen-activated protein kinase 1/2, has shown promise in treating various cancers. This study evaluated the safety and efficacy of the Phase III formulation of selumetinib capsules in healthy subjects.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

7.

Effects of cytochrome P450 (CYP3A4 and CYP2C19) inhibition and induction on the exposure of selumetinib, a MEK1/2 inhibitor, in healthy subjects: results from two clinical trials.

Author: DymondAngela W, SoKaren, MartinPaul, HuangYifan, SeverinPaul, MathewsDavid, LisbonEleanor, MarianiGabriella

Drug interactions

These two phase I studies investigated the effect of co-administering selumetinib, a cancer drug, with CYP3A4/CYP2C19 inhibitors (itraconazole/fluconazole) or a CYP3A4 inducer (rifampicin) on its pharmacokinetics and safety.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

8.

Dermatologic side effects associated with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886).

Author: BalagulaYevgeniy, Barth HustonKatherine, BusamKlaus J, LacoutureMario E, ChapmanPaul B, MyskowskiPatricia L

Cancer treatment
Dermatologic toxicities

This review discusses the dermatological toxicities associated with selumetinib, a MEK inhibitor currently in clinical trials for various solid malignancies. It explores the clinical presentation, evolution, and management of these toxicities.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Development of a MEK inhibitor, NFX-179, as a chemoprevention agent for squamous cell carcinoma.

Author: SarinKavita Y, KincaidJohn, SellBrittney, ShahryariJahanbanoo, DunctonMatthew A J, MorefieldElaine, SunWenchao, PrietoKarol, Chavez-ChiangOmar, de Moran SeguraCarlos, NguyenJonathan, BronsonRoderick T, PlotkinScott R, KochendoerferGerd G, FennPeter, WoottonMichael A, PowalaChristopher, de SouzaMark P, TsaiKenneth Y

NFX-179 cSCC chemoprevention
Topical MEK inhibition

This study investigated the potential of topical MEK inhibition using NFX-179 for the chemoprevention of cutaneous squamous cell carcinoma (cSCC). NFX-179, a metabolically labile MEKi, was found to potently and selectively suppress the MAPK pathway in the skin before rapid metabolism in the systemic circulation. Topical application of NFX-179 gel reduced the formation of new cSCCs in a mouse model by an average of 60% at doses of 0.1% and greater. No toxicities were observed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes.

Author: LiuSi-Qing, ChenDing-Yuan, LiBei, GaoZhi-Jie, FengHong-Fang, YuXin, LiuZhou, WangYuan, LiWen-Ge, SunSi, SunSheng-Rong, WuQi

Prognosis prediction
Treatment targets
Cancer progression

This study analyzed adipocyte subtypes in the tumor-adipose microenvironment (TAME) using single-cell RNA sequencing. It identified several cancer-associated adipocyte subtypes, including DPP4+ and CD36+, that were linked to poor overall survival. These subtypes may serve as prognostic predictors and potential targets for future cancer treatments.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis.

Author: TongJiajia, LiYan, CaiXiaojie, LouFangzhou, SunYang, WangZhikai, ZhengXichen, ZhouHong, ZhangZiyang, FangZilong, DingWenxiang, DengSiyu, XuZhenyao, NiuXiaoyin, WangHonglin

Mast cell inhibition
Skin barrier homeostasis
Skin inflammation relief

This study explored the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-β-boswellic acid (CKBA) on atopic dermatitis (AD). CKBA suppressed mast cell activation in AD via the ERK signaling pathway, demonstrating its potential as a therapeutic candidate drug for AD.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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