Effects of temsirolimus: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Temsirolimus is an mTOR (mechanistic target of rapamycin) inhibitor. mTOR is a protein that plays an important role in cell growth and proliferation. By inhibiting mTOR, temsirolimus can suppress cancer cell growth. Temsirolimus has been used to treat various cancers such as renal cancer, breast cancer, and neuroendocrine tumors, and its effectiveness has been demonstrated. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14

Temsirolimus not only has a direct effect on cancer cells but also affects immune cells, suggesting the possibility of promoting the immune response to cancer. 13

Temsirolimus may be able to treat cancer more effectively when used in combination with other drugs. 12 , 20 , 4 , 6 , 7 , 1

Temsirolimus may also affect normal cells. 10 , 9 , 2 , 16 , 20 , 21

Benefits and Risks

Benefit Summary

Temsirolimus has been shown to suppress cancer cell growth. It also suggests the possibility of promoting the immune response to cancer. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14 , 13

Temsirolimus may be able to treat cancer more effectively when used in combination with other drugs. 12 , 20 , 4 , 6 , 7 , 1

Risk Summary

Temsirolimus may also affect normal cells. 10 , 9 , 2 , 16 , 20 , 21

Comparison of Studies

Commonalities of Studies

In many studies, temsirolimus has been found to be effective in suppressing cancer cell growth. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14

Differences in Studies

Studies differ in the types of cancer temsirolimus is effective for and the degree of side effects. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14 , 10 , 9 , 2 , 16 , 20 , 21

Consistency and Contradictions of the Findings

The effectiveness of temsirolimus varies depending on the type of cancer and the patient's condition. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14 , 10 , 9 , 2 , 16 , 20 , 21

Cautions Regarding Practical Application

Temsirolimus is a drug used to treat cancer. When receiving cancer treatment, be sure to consult your doctor and follow their instructions. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14

Limitations of Current Research

The effects and side effects of temsirolimus are not yet fully understood. Further research is needed. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14 , 10 , 9 , 2 , 16 , 20 , 21

Future Research Directions

Further research is needed to better understand the effects of temsirolimus. In particular, it is necessary to investigate how temsirolimus suppresses cancer cell growth, what side effects it has, and its combined effects with other drugs. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14 , 10 , 9 , 2 , 16 , 20 , 21

Conclusion

Temsirolimus is a drug used to treat cancer. Its effectiveness has been recognized, but it may have side effects. When receiving cancer treatment, be sure to consult your doctor and follow their instructions. 11 , 8 , 5 , , 15 , 17 , 7 , 3 , 19 , 14 , 10 , 9 , 2 , 16 , 20 , 21

Literature analysis of 22 papers
Positive Content
20
Neutral Content
0
Negative Content
2
Article Type
3
1
2
2
21
1.

A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab-resistant head and neck cancer: The MAESTRO study.

Author: SeiwertTanguy Y, KochannySara, WoodKevin, WordenFrancis P, AdkinsDouglas, WadeJames L, SleckmanBethany G, AndersonDaniel, BrissonRyan J, KarrisonTheodore, StadlerWalter M, VokesEverett E

HNSCC treatment

This study explored the potential of combining two drugs to overcome resistance to the cancer drug cetuximab in head and neck cancer. The study is based on the idea that blocking two key pathways involved in cancer cell growth might be more effective than blocking just one.

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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

2.

Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR.

Author: ZhangXiaoli, ChenWei, GaoQiong, YangJunsheng, YanXueni, ZhaoHan, SuLin, YangMeimei, GaoChenlang, YaoYao, InokiKen, LiDan, ShaoRong, WangShiyi, SahooNirakar, KudoFumitaka, EguchiTadashi, RuanBenfang, XuHaoxing

Cancer treatment
Neurodegeneration treatment

Rapamycin, a drug used to treat cancer and neurodegeneration, has been shown to activate TRPML1, a calcium release channel in lysosomes, leading to increased autophagy. This process helps clear damaged cells and may contribute to the drug's neuroprotective and anti-aging effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

3.

Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features.

Author: BellmuntJ, SzczylikC, FeingoldJ, StrahsA, BerkenblitA

Prolonged survival
Temsirolimus-related side effects

This study reviewed adverse events associated with temsirolimus, a mammalian target of rapamycin inhibitor, in patients with advanced renal cell carcinoma. Temsirolimus was effective in extending survival, but it was associated with a range of side effects.

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

6.

A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas.

Author: PirosaMaria C, ZhangLu, HitzFelicitas, NovakUrban, HessDagmar, TerrotTatiana, PascaleMariarosa, MazzucchelliLuca, BertoniFrancesco, CavalliFranco, ZuccaEmanuele, StathisAnastasios

Lymphoma treatment
Hyperphosphatemia
Hypertriglyceridemia
Lymphopenia
Neutropenia
Thrombocytopenia

This phase I trial evaluated the safety, tolerability, and activity of inotuzumab ozogamicin combined with temsirolimus for relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Dose-limiting toxicities were observed, limiting the therapeutic potential of this combination.

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

Language : English

8.

Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Author: MascarenhasLeo, ChiYueh-Yun, HingoraniPooja, AndersonJames R, LydenElizabeth R, RodebergDavid A, IndelicatoDaniel J, KaoSimon C, DasguptaRoshni, SpuntSheri L, MeyerWilliam H, HawkinsDouglas S

Superior EFS
Temsirolimus effective

Temsirolimus showed a superior event-free survival compared to bevacizumab in patients with rhabdomyosarcoma (RMS) in first relapse.

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.
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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

The Route to 'Chemobrain' - Computational probing of neuronal LTP pathway.

Author: FahimAmmad, RehmanZaira, BhattiMuhammad Faraz, VirkNasar, AliAmjad, RashidAmir, ParachaRehan Zafar

Cognitive impairment

This study investigates the potential off-target interactions of chemotherapeutic drugs with proteins involved in neuronal long-term potentiation (LTP). Several drugs were identified as potential LTP pathway inhibitors, suggesting possible interference with neurotransmission and synaptic plasticity in cancer patients receiving chemotherapy.

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.

Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.

Author: AlammarHajar, NassaniRayan, AlshehriMana M, AljohaniAlaa A, AlrfaeiBahauddeen M

Medulloblastoma treatment
Drug resistance

This review highlights the mechanisms of resistance to mTOR inhibitors in medulloblastoma, a common fatal pediatric brain tumor, and suggests the importance of combination therapy due to its highly resistant nature.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

12.

Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer.

Author: HeJichao, McLaughlinRonan P, van der NoordVera, FoekensJohn A, MartensJohn W M, van WestenGerard, ZhangYinghui, van de WaterBob

TNBC treatment

Triple-negative breast cancer (TNBC) is a difficult-to-treat type of breast cancer, and current treatments are not very effective. New therapies that target multiple cancer pathways are being studied to improve outcomes for TNBC patients.

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

Language : English

13.

Different immunological effects of the molecular targeted agents sunitinib, everolimus and temsirolimus in patients with renal cell carcinoma.

Author: KobayashiYukari, YamadaDaisuke, KawaiTaketo, SatoYusuke, TeshimaTaro, YamadaYuta, NakamuraMasaaki, SuzukiMotofumi, MatsumotoAkihiko, NakagawaTohru, HosoiAkihiro, NagaokaKoji, KarasakiTakahiro, MatsushitaHirokazu, KumeHaruki, KakimiKazuhiro

Cancer immunotherapy
Immune-related toxicity

Molecular targeted agents like sunitinib, everolimus, and temsirolimus have different immunological effects in patients with renal cell carcinoma (RCC). Temsirolimus showed potential for combination therapies with other immunomodulators.

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

Language : English

14.

A phase II evaluation of temsirolimus with carboplatin and paclitaxel followed by temsirolimus consolidation in clear cell ovarian cancer: An NRG oncology trial.

Author: FarleyJohn H, BradyWilliam E, O'MalleyDavid, FujiwaraKeiichi, YonemoriKan, BonebrakeAlbert, SecordAngeles Alvarez, StephanJean-Marie, WalkerJoan L, NamJoo-Hyun, BirrerMichael J, GershensonDavid M

Well tolerated

The carboplatin/paclitaxel + temsirolimus regimen was well tolerated in patients with newly diagnosed clear cell ovarian cancer (CCOC). In optimally debulked patients, 54% had a PFS >12 months, but the regimen did not statistically significantly increase PFS at 12 months compared to historical controls.

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

15.

Effects of Tyrosine Kinase Inhibitors on Blood Pressure in Patients with Unresectable or Advanced Recurrent Renal Cell Carcinoma-Bayes-Mixed Treatment Comparison Meta-Analysis.

Author: YamaguchiShion, MurayamaRumi, SatohEisaku, InoueTadao, IseYuya

Treats renal cell carcinoma
Hypertension

This study clinically evaluated five tyrosine kinase inhibitors (TKIs) used to treat renal cell carcinoma in Japan using Bayes-mixed treatment comparison meta-analysis. The study aimed to develop a decision-making model for selecting the optimal TKI based on its effects on blood pressure and response rate.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

16.

A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors.

Author: ParkHaeseong, WilliamsKerry, TrikalinosNikolaos A, LarsonSarah, TanBenjamin, WaqarSaiama, SureshRama, MorgenszternDaniel, Van TineBrian A, GovindanRamaswamy, LuoJingqin, LockhartA Craig, Wang-GillamAndrea

Tumor regression
EGFR activation
mTOR resistance

Resistance to mammalian target of rapamycin (mTOR) inhibitors is partly due to epidermal growth factor receptor (EGFR) activation. This phase I study aims to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors.

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.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Mood-stabilizing effects of rapamycin and its analog temsirolimus: relevance to autophagy.

Author: KaraNirit Z, Flaisher-GrinbergShlomit, AndersonGrant W, AgamGalila, EinatHaim

Mood stabilization

Pharmacological enhancement of autophagy may have mood-stabilizing effects. In mice, rapamycin, an mTOR inhibitor and autophagy enhancer, reduced mania-like behaviors, and temsirolimus, another autophagy enhancer, reduced depression-related immobility.

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.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

19.

Use of <i>Ex</i> <i>Vivo</i> Patient-Derived Tumor Organotypic Spheroids to Identify Combination Therapies for <i>HER2</i> Mutant Non-Small Cell Lung Cancer.

Author: IvanovaElena, KuraguchiMari, XuMan, PortellAndrew J, TausLuke, DialaIrmina, LalaniAlshad S, ChoiJihyun, ChambersEmily S, LiShuai, LiuShengwu, ChenTing, BarbieThanh U, OxnardGeoffrey R, HaworthJacob J, WongKwok-Kin, DahlbergSuzanne E, ArefAmir A, BarbieDavid A, BahcallMagda, PaweletzCloud P, JännePasi A

Drug screening

This study investigated the potential of using patient-derived organotypic spheroids (XDOTS) to identify drug combinations for HER2 mutant non-small cell lung cancer (NSCLC).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination.

Author: BlázquezCristina, Ruiz-CalvoAndrea, Bajo-GrañerasRaquel, BaufretonJérôme M, ReselEva, VarilhMarjorie, Pagano ZottolaAntonio C, MarianiYamuna, CannichAstrid, Rodríguez-NavarroJosé A, MarsicanoGiovanni, Galve-RoperhIsmael, BellocchioLuigi, GuzmánManuel

Rescued motor coordination
Motor impairment

Cannabis use is increasing worldwide. This study investigated the effects of &#916;<sup>9</sup>-tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis, on motor function. THC was found to disrupt autophagy, a process that helps to remove damaged cells, in the striatum, a brain region involved in movement. This disruption led to impaired motor coordination in mice. Increasing autophagy through medication or diet was found to improve motor coordination. These findings suggest that therapies aimed at enhancing autophagy may be helpful for reducing the negative effects of cannabis on motor function.

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

21.

The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review.

Author: LinHong, SalechFelipe, LimAnthony, VogrinSara, DuqueGustavo

Bone resorption inhibition
Clinical improvement
Reduced muscle protein synthesis

Rapalogues show potential therapeutic benefits for age-related musculoskeletal disorders (MSKD) in humans, including decreased bone resorption and improved rheumatoid arthritis outcomes. However, further research is needed to confirm its efficacy and understand its impact on osteoporosis, sarcopenia, and osteosarcopenia.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells.

Author: KimSeo Yun, JeongEun-Hui, LeeTae-Gul, KimHye-Ryoun, KimCheol Hyeon

Increased radiosensitivity

Combining trametinib and temsirolimus with radiation enhanced radiosensitivity in non-small-cell lung carcinoma cells.

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

Language : English

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