Effects of dabrafenib: A Synthesis of Findings from 17 Studies

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Original Abstract of the Article

Major Research Findings

Dabrafenib is a BRAF inhibitor used in the treatment of cancers like melanoma. Numerous studies have shown its effectiveness. For instance, 6 found that combining dabrafenib with MEK inhibitors produced potent molecular and immunological effects in NRAS-mutant melanoma cells. This combination therapy successfully inhibited melanoma cell growth, induced apoptosis, and altered the expression of immune regulatory molecules. Additionally, 16 demonstrated that dabrafenib protected mice from hearing loss caused by cisplatin. Dabrafenib not only protected mice from cisplatin-induced hearing damage but also reduced weight loss associated with cisplatin. These results suggest dabrafenib holds promise as a drug to prevent cisplatin-induced hearing loss.

Benefits and Risks

Benefits Summary

Dabrafenib is an effective drug for treating cancers like BRAF-mutant melanoma. Moreover, it has been shown to protect mice from hearing loss caused by cisplatin. These results suggest dabrafenib has potential therapeutic benefits in both cancer treatment and hearing loss prevention.

Risks Summary

Dabrafenib may cause side effects like skin rashes, digestive problems, and liver damage. It can also interact with other medications. It is crucial to discuss the risks and benefits with your doctor before using dabrafenib. Following your doctor's instructions is essential to minimize the risks associated with using this drug.

Comparison Between Studies

Commonalities

Several studies indicate the effectiveness of dabrafenib in cancer treatment. It has been shown to work synergistically when combined with other drugs. Furthermore, dabrafenib may mitigate side effects associated with other medications.

Differences

The effectiveness and incidence of side effects from dabrafenib may vary across studies. This could be attributed to differences in the patients and tumors studied, the dosage and administration methods of dabrafenib, and differences in the study methodologies and data analysis approaches.

Consistency and Contradictions in Results

Many studies support the effectiveness of dabrafenib in cancer treatment. However, some studies have reported limited effectiveness and pronounced side effects. It's crucial to approach these findings with caution. Dabrafenib may not be effective for all patients. Careful consideration of the patient's condition, tumor type, dabrafenib dosage, and administration methods is crucial for selecting the right treatment.

Points to Note for Real-World Application

Dabrafenib should only be used under a doctor's guidance. Do not self-medicate or change your dosage or administration method without consulting a doctor. Dabrafenib can interact with other medications. Inform your doctor if you're currently taking other medications. Dabrafenib can cause side effects. Consult your doctor if you experience any side effects.

Current Research Limitations

Research on dabrafenib is still in its early stages. Future studies need to further explore its effectiveness and safety. Additionally, research is needed to elucidate dabrafenib's mechanism of action and develop more effective treatment methods.

Future Research Directions

Future research on dabrafenib should include detailed investigations into its effectiveness and safety. Understanding its mechanism of action and developing more effective treatment methods is crucial. Additionally, researching ways to mitigate side effects associated with dabrafenib is essential.

Conclusion

Dabrafenib is an effective drug for treating cancers like BRAF-mutant melanoma. However, it can cause side effects. It's vital to discuss risks and benefits with your doctor before using dabrafenib. Following your doctor's instructions is crucial to minimize the risks associated with using this drug. Future research should include detailed investigations into its effectiveness and safety. Additionally, researching ways to mitigate side effects associated with dabrafenib is essential.

Literature analysis of 17 papers
Positive Content
16
Neutral Content
0
Negative Content
1
Article Type
1
0
0
0
14
3.

Therapeutic inhibition of ATR in differentiated thyroid cancer.

Author: LinShu-Fu, LeeYi-Yin, WuMing-Hsien, LuYu-Ling, YehChun-Nan, ChenWei-Yi, ChouTing-Chao, WongRichard J

Improved DTC treatment
Reduced tumor growth
Drug side effects

BAY 1895344, an ATR inhibitor, exhibited anti-tumor activity in differentiated thyroid cancer (DTC) cell lines and xenograft models. The combination of BAY 1895344 with other therapies showed synergistic effects, providing rationale for further clinical investigation.

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

4.

Targeting SHP2 reverses BRAF inhibitor tolerance in anaplastic thyroid carcinoma.

Author: TangTao, ZhouJie, ZhangLi-Xin, YangGang, LiWei-Nan, ZhuJian-Jiao, XiongYong-Fu, LiJing-Dong

ATC treatment
Dabrafenib resistance reversal
Dabrafenib resistance

The combination of dabrafenib and SHP2 inhibitor (SHP099) reversed dabrafenib resistance in anaplastic thyroid carcinoma (ATC) cells by inhibiting the RAS signaling pathway.

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

Language : English

6.

BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS-mutant melanoma cells: Insights into mode of action and resistance mechanisms.

Author: DinterLisa, KaritzkyPaula C, SchulzAlexander, WurmAlexander A, MehnertMarie-Christin, SergonMildred, TungerAntje, LescheMathias, WehnerRebekka, MüllerAnja, KäublerTheresa, NiessnerHeike, DahlAndreas, BeissertStefan, SchmitzMarc, MeierFriedegund, SeligerBarbara, WestphalDana

Effective melanoma treatment
Resistance development

This study investigated the molecular and immunological effects of BRAF/MEK inhibitor combinations in sensitive NRAS-mutant melanoma cells. The combinations demonstrated potent antiproliferative, proapoptotic, and immunostimulatory effects, potentially offering new treatment strategies for NRAS-mutant melanoma. However, the study also identified mechanisms of resistance that may hinder treatment efficacy.

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

Language : English

8.

[Unusual association of BRAF and MEK inhibitors: Clinical response of metastatic melanoma treated with dabrafenib-cobimetinib].

Author: LeenhardtFanny, MbatchiLitaty, EvrardAlexandre, CupissolDidier, LesageCandice

Melanoma treatment
Adverse events

A patient with metastatic melanoma achieved complete remission for 19 months using an off-label combination of dabrafenib (BRAFi) and cobimetinib (MEKi). This unusual combination was used to manage pyrexia and was closely monitored using therapeutic drug monitoring. This case report highlights the potential benefit of personalized treatment strategies in melanoma management.

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.
English AbstractA summary of a research paper/publication written in English for a wider audience.
LetterA written message for communication and exchange of information between individuals.

Language : French

9.

Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory <i>BRAF</i> V600-Mutant Pediatric High-Grade Glioma.

Author: HargraveDarren R, TerashimaKeita, HaraJunichi, KordesUwe R, UpadhyayaSanthosh A, SahmFelix, BouffetEric, PackerRoger J, WittOlaf, SandalicLarissa, KielochAgnieszka, RussoMark, CohenKenneth J,

Treatment for BRAF V600-mutant pHGGs

This study aims to investigate the efficacy of dabrafenib, a BRAF inhibitor, in treating pediatric high-grade gliomas (pHGGs) with BRAF V600 mutations. Dabrafenib has shown activity in previous trials for relapsed/refractory BRAF V600-mutant HGGs in children and adults.

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

Language : English

10.

Dabrafenib alters MDSC differentiation and function by activation of GCN2.

Author: CiudadM Teresa, QuevedoRene, LamorteSara, JinRobbie, NziroreraNadine, KoritzinskyMarianne, McGahaTracy L

Attenuated MDSC suppression
Reduced PMN-MDSCs

This study investigated the effect of the BRAF inhibitor dabrafenib on myeloid-derived suppressor cell (MDSC) differentiation and function. Dabrafenib was found to attenuate MDSC suppressive activity through GCN2 activation, which blocked the transition to PMN-MDSCs and resulted in their loss.

PreprintAn early version of a research paper before it is peer-reviewed. It aims to share research with the community early on.

Language : English

11.

Activated MKK3/MYC crosstalk impairs dabrafenib response in BRAFV600E colorectal cancer leading to resistance.

Author: PrantedaAngelina, PiastraValentina, SerraMartina, BernardiniRoberta, Lo SardoFederica, CarpanoSilvia, DiodoroMaria Grazia, BartolazziArmando, MilellaMichele, BlandinoGiovanni, BossiGianluca

Potential novel therapeutic opportunities

This study investigated the role of MKK3 in BRAF inhibitor resistance in colorectal cancer (CRC) cells with BRAF mutations. The findings suggest that MKK3 activation contributes to resistance and that targeting MKK3 could be a promising therapeutic strategy for BRAF<sup>V600E</sup> CRC.

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

Language : English

12.

A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAF<sup>V600</sup> mutant advanced melanoma (INTERIM).

Author: DayimuAlimu, GuptaAvinash, MatinRubeta N, NobesJenny, BoardRuth, PayneMiranda, RaoAnkit, FusiAlberto, DansonSarah, EcclesBryony, CarserJudith, BrownCiara O'Hanlon, StevenNeil, BhattacharyyaMadhumita, BrownEwan, GonzalezMichael, HighleyMartin, PickeringLisa, KumarSatish, WaterstonAshita, BurghelGeorge, DemainLeigh, BakerEleanor, WulffJerome, QianWendi, TwelvesSophie, MiddletonMark, CorriePippa

Life expectancy extension
Melanoma treatment
Acquired resistance

INTERIM, a phase 2 trial, evaluated an intermittent dosing regimen of BRAF+MEK inhibitors for patients with BRAF<sup>V600</sup> mutant advanced melanoma. Intermittent dosing showed promising results in overcoming acquired resistance, extending the benefit duration of these inhibitors.

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

Language : English

16.

Dabrafenib protects from cisplatin-induced hearing loss in a clinically relevant mouse model.

Author: IngersollMatthew A, LutzeRichard D, PushpanChithra K, KelmannRegina G, LiuHuizhan, MayMark T, HunterWilliam J, HeDavid Zz, TeitzTal

Reduced hearing loss

Dabrafenib, an FDA-approved BRAF kinase inhibitor, effectively protected against cisplatin-induced hearing loss in mice. It provided significant hearing protection lasting four months, with a good therapeutic index and reduced cisplatin-induced weight loss. Dabrafenib shows potential as a drug for preventing cisplatin-induced hearing loss.

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

Language : English

17.

Effects of particle size, food, and capsule shell composition on the oral bioavailability of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors.

Author: OuelletDaniele, GrossmannKenneth F, LimentaniGiselle, NebotNoelia, LanKevin, KnowlesLara, GordonMichael S, SharmaSunil, InfanteJeffrey R, LorussoPatricia M, PandeGirish, KracheyElizabeth C, BlackmanSamuel C, CarsonStanley W

Melanoma treatment

Dabrafenib is a drug being developed for melanoma. This study investigated the effect of food and drug formulation on the absorption of dabrafenib.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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