Effects of dasatinib: A Synthesis of Findings from 28 Studies

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Original Abstract of the Article

Major Research Findings

Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML). 23 It has been shown to have anti-tumor effects in a variety of cancers, including CML, oral cancer, and breast cancer. 13 26 2 Dasatinib has also been shown to have immunomodulatory effects, inhibiting T cell activation and promoting the expansion of NK cells. 23 14 19 In addition, dasatinib has been shown to have anti-angiogenic effects. 13 25 In a preclinical trial using nonhuman primates, dasatinib combined with quercetin was found to reduce senescence markers in adipose tissue and improve immune cell profiles. 3 The combination also showed renal benefits and improved metabolic health when combined with caloric restriction. 3

Studies have shown that dasatinib can also cause side effects, including gastrointestinal bleeding and liver toxicity. 15 Dasatinib can also cause cardiac myocyte damage through the inhibition of the RAF/MEK/ERK pro-survival pathway. 18 Other potential side effects of dasatinib include colitis, hyperglycemia, and hypertriglyceridemia. 16 21

Benefits and Risks

Benefit Summary

Dasatinib is an effective treatment for CML. 23 It has been shown to inhibit CML cell proliferation and induce apoptosis. 9 13 Dasatinib also has anti-angiogenic effects, which may help to slow the growth of tumors. 13 Dasatinib has immunomodulatory effects, inhibiting T cell activation and promoting the expansion of NK cells. 23 14 19 A preclinical trial using nonhuman primates suggests that dasatinib combined with quercetin may improve aging outcomes, reducing senescence markers and improving immune cell profiles. 3 The combination also showed renal benefits and improved metabolic health when combined with caloric restriction. 3

Risk Summary

Dasatinib can cause a variety of side effects, including gastrointestinal bleeding, liver toxicity, cardiac myocyte damage, colitis, hyperglycemia, and hypertriglyceridemia. 15 18 16 21

Comparison of Studies

Commonalities

Multiple studies demonstrate dasatinib's efficacy in inhibiting tumor cell proliferation and inducing apoptosis. 9 13 27 Moreover, its immunomodulatory effects, impacting T cell activation and NK cell expansion, are consistently reported. 23 19 14 Additionally, its anti-angiogenic properties are noted in several studies. 13 25

Differences

Dasatinib's immunomodulatory effects are complex and vary across studies. While some studies show its ability to promote NK cell expansion, others highlight its inhibitory effects on T cell activation. 23 19 14 5 These inconsistencies might stem from factors like patient conditions, dosage, or specific T cell subsets investigated.

Consistency and Contradictions

Dasatinib demonstrates consistent efficacy in inhibiting tumor growth and inducing apoptosis in various cancers. 9 13 Its anti-angiogenic properties also show consistency across studies. 13 However, its immunomodulatory effects present a degree of contradiction, with differing observations regarding its influence on T cell activation and NK cell expansion. 23 19 14 5 This inconsistency highlights the need for further investigation to understand how dasatinib's immunomodulatory effects are influenced by patient conditions and dosages.

Considerations for Real-World Application

Dasatinib is a promising drug for treating CML. 23 However, it is important to be aware of its potential side effects. 15 18 16 21 If you are considering taking dasatinib, it is important to talk to your doctor about the risks and benefits. They can help you determine if dasatinib is the right treatment for you.

Limitations of Current Research

More research is needed to fully understand the effects of dasatinib. The immunomodulatory effects of dasatinib are complex and vary across studies. 23 19 14 5 Further research is needed to determine how dasatinib's immunomodulatory effects are influenced by patient conditions, dosages, and specific T cell subsets. Additional research is also needed to investigate the potential benefits and risks of dasatinib in combination with other therapies. 26 25 28 17

Future Research Directions

Future research should focus on understanding the complex immunomodulatory effects of dasatinib. This includes investigating how patient conditions and dosages influence these effects. 23 19 14 5 Researchers should also explore the potential benefits and risks of dasatinib in combination with other therapies. 26 25 28 17

Conclusion

Dasatinib is a promising drug for treating CML. 23 It has been shown to be effective in inhibiting tumor cell proliferation and inducing apoptosis. 9 13 It also has anti-angiogenic effects and immunomodulatory effects, potentially contributing to better outcomes for patients. 13 23 19 14 However, it is important to be aware of its potential side effects and to discuss them with your doctor. 15 18 16 21 Further research is needed to fully understand the effects of dasatinib and to explore its potential in combination with other therapies.

Literature analysis of 28 papers
Positive Content
25
Neutral Content
0
Negative Content
3
Article Type
0
0
0
1
28
3.

Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design.

Author: RuggieroAlistaire D, VemuriRavichandra, BlawasMegan, LongMasha, DeStephanisDarla, WilliamsAbigail G, ChenHaiying, JusticeJamie N, MacauleyShannon L, DaySteven M, KavanaghKylie

Improved immune cells
Improved metabolic health
Reduced senescence

This study investigated the effects of the senolytic combination dasatinib and quercetin in a middle-aged nonhuman primate model. The combination reduced senescence marker gene expressions and improved immune cell profiles and intestinal barrier function.

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

4.

Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism.

Author: RaishMohammad, AhmadAjaz, ShahidMudassar, JardanYousef A Bin, AhadAbdul, KalamMohd Abul, AnsariMushtaq Ahmad, IqbalMuzaffar, AliNaushad, AlkharfyKhalid M, Al-JenoobiFahad I

CML treatment
Herb-drug interactions

Dasatinib, a drug used to treat leukemia, can interact with apigenin, a common dietary compound found in herbs and food. This study found that apigenin significantly altered the pharmacokinetics of dasatinib, potentially increasing its levels in the body. This could lead to serious side effects and highlight the importance of considering herb-drug interactions when prescribing dasatinib.

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

Language : English

5.

Differential inhibition of T-cell receptor and STAT5 signaling pathways determines the immunomodulatory effects of dasatinib in chronic phase chronic myeloid leukemia.

Author: HarringtonPatrick, DillonRichard, RadiaDeepti, RousselotPhilippe, McLornanDonal P, OngMark, GreenAnna, VerdeAlessandro, HussainFarzana, RajKavita, KordastiShahram, HarrisonClaire, De LavalladeHugues

Enhanced tumor immunity
T cell modulation
T cell suppression

Dasatinib is a drug that inhibits the SRC kinase LCK, which is involved in T-cell receptor signaling. This study found that dasatinib can selectively deplete regulatory T cells (Tregs) and enhance anti-tumor immunity in patients with chronic myeloid leukemia.

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

6.

Effects of the STAMP-inhibitor asciminib on T cell activation and metabolic fitness compared to tyrosine kinase inhibition by imatinib, dasatinib, and nilotinib.

Author: HäselbarthLukas, KarowAxel, MentzKristin, BöttcherMartin, Roche-LancasterOisin, KrumbholzManuela, JitschinRegina, MougiakakosDimitrios, MetzlerMarkus

CML treatment
Immune reconstitution

Asciminib, a novel BCR::ABL1 fusion protein inhibitor, shows milder inhibitory effects on T cell activation compared to other tyrosine kinase inhibitors (TKIs). This suggests potential benefits for immune reconstitution and control of residual chronic myeloid leukemia (CML) cells.

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

Language : English

11.

A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities.

Author: NekoukarZahra, MoghimiMinoo, SalehifarEbrahim

Cytogenetic response
Hematologic response
Improved CML treatment
Pleural effusion
Pulmonary complications
Pulmonary hypertension

This narrative review scrutinizes the pulmonary complications of dasatinib and focuses on the management of these toxicities.

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

12.

Antidiabetic Effects of the Senolytic Agent Dasatinib.

Author: SalaamiOmid, KuoChia-Ling, DrakeMatthew T, KuchelGeorge A, KirklandJames L, PignoloRobert J

Reduced blood glucose
Reduced insulin units
Weight loss

Dasatinib, a senolytic agent, showed antidiabetic effects comparable to contemporary diabetic treatments in older patients with type 2 diabetes mellitus.

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

13.

Anti-growth and pro-apoptotic effects of dasatinib on human oral cancer cells through multi-targeted mechanisms.

Author: ParkNam-Sook, ParkYu-Kyung, YadavAnil Kumar, ShinYoung-Min, Bishop-BaileyDavid, ChoiJong-Soon, ParkJong Wook, JangByeong-Churl

Anti-angiogenic effect
Oral cancer suppression

Dasatinib, a Src inhibitor, demonstrated strong anti-growth, anti-angiogenic, and pro-apoptotic effects in human oral cancer cells. It suppressed growth, induced apoptosis, and inhibited phosphorylation of multiple targets including Src, EGFR, STAT-3, STAT-5, PKB, and ERK-1/2. Dasatinib also exhibited anti-angiogenic properties by reducing HIF-1α expression and stability.

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

14.

[Effects of Dasatinib on the Expansion, Subsets, Receptor Expression and Cytotoxic Function of NK Cells in Vitro].

Author: ShengLi-Xia, WangJia-Ping, LaiYan-Li, WuHao, SunYong-Cheng, ZhouMiao, OuyangGui-Fang, HuangHe

NK cell cytotoxicity
NK cell expansion

Dasatinib, at a concentration of 20 nmol/L, increases the amplification efficiency of NK cells in vitro, upregulates the expression of NK activating receptors, and increases NK cytotoxicity against leukemia cell line K562 cells.

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

Language : Chinese

16.

Dasatinib-induced colitis: discovering the side effects of immunotherapy.

Author: Jiménez BeltránVíctor, Bermúdez AlarcónAuxiliadora, Castaño FernándezOlegario

Colitis

This case report describes a patient with chronic myeloid leukemia who developed colitis after receiving dasatinib, an immunotherapy drug. The case highlights the importance of recognizing and detecting cases of drug-induced colitis, particularly in patients receiving immunomodulatory medications.

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

19.

Innate T-αβ lymphocytes as new immunological components of anti-tumoral "off-target" effects of the tyrosine kinase inhibitor dasatinib.

Author: BarbarinAlice, AbdallahMyriam, LefèvreLucie, PiccirilliNathalie, CayssialsEmilie, RoyLydia, GombertJean-Marc, HerbelinAndré

Cancer therapy
Chemoimmunotherapy
Immune stimulation

This study investigates the potential immunostimulatory effects of dasatinib, a tyrosine kinase inhibitor, on innate T-αβ cells. The results suggest that dasatinib may activate iNKT cells and innate-memory CD8 T-cells, opening new opportunities for chemoimmunotherapy.

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

Language : English

20.

Immediate Effects of Dasatinib on the Migration and Redistribution of Naïve and Memory Lymphocytes Associated With Lymphocytosis in Chronic Myeloid Leukemia Patients.

Author: Colom-FernándezBeatriz, KreutzmanAnna, Marcos-JiménezAna, García-GutiérrezValentín, Cuesta-MateosCarlos, Portero-SainzItxaso, Pérez-GarcíaYaiza, CasadoLuis Felipe, Sánchez-GuijoFermín, Martínez-LópezJoaquín, AyalaRosa M, BoquéConcha, XicoyBlanca, MonteroIsabel, SotoCésar, PazRaquel, SilvaGabriela, Vega-PirisLorena, SteegmannJuan Luis, Muñoz-CallejaCecilia

Better clinical response

This study investigated the effects of dasatinib, a drug used to treat chronic myeloid leukemia (CML), on lymphocyte migration. The researchers found that dasatinib intake inhibits T-cell migration toward certain chemokines, suggesting that dasatinib might redistribute lymphocytes within the body. This may contribute to the lymphocytosis (high lymphocyte count) that is often seen in patients taking dasatinib.

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

Language : English

22.

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma.

Author: CastilloLesley, YoungAdelaide I J, MawsonAmanda, SchafranekPia, SteinmannAngela M, NessemDanielle, ParkinAshleigh, JohnsAmber, ChouAngela, LawAndrew M K, LucasMorghan C, MurphyKendelle J, DengNiantao, Gallego-OrtegaDavid, CaldonCatherine E, , TimpsonPaul, PajicMarina, OrmandyChristopher J, OakesSamantha R

Reduced metastasis
Reduced tumor growth

Targeting both MCL-1 and SRC proteins in pancreatic ductal adenocarcinoma (PDAC) may be a promising therapeutic strategy. This study shows that combining an MCL-1 antagonist with the SRC inhibitor dasatinib reduces tumor growth and metastasis in preclinical models.

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

23.

Effects of dasatinib on CD8<sup>+</sup>T, Th1, and Treg cells in patients with chronic myeloid leukemia.

Author: WeiXiaoqing, HeLin, WangXiaodong, LinMin, DaiJingying

Increased Th1 and CD8 cells
None

Dasatinib, a tyrosine kinase inhibitor (TKI), may increase Th1 and CD8

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

Language : English

25.

Anti-glioma Effects of Caffeic Acid Phenethyl Ester and Dasatinib Combination Therapy in an in vivo Rat Glioma Model.

Author: BalkhiHenah Mehraj, HaqEhtishamul, GulTaseen, SanaSyed

Low drug resistance
Reduced glioma proliferation

The combination of CAPE and Dasatinib significantly reduced the proliferation of glioma cells in vivo. This suggests that this therapy may be a promising treatment for gliomas.

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

Language : English

27.

Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562 cells.

Author: DamianoSara, MontagnaroSerena, PuzioMaria V, SeverinoLorella, PagniniUgo, BarbarinoMarcella, CesariDaniele, GiordanoAntonio, FlorioSalvatore, CiarciaRoberto

CML treatment
ROS generation
SERCA receptor functionality

Resveratrol, rMnSOD and δ-tocotrienol reduced lipid peroxidation induced by Nilotinib (NIL) and Dasatinib (DAS), two tyrosine kinase inhibitors for chronic myeloid leukemia. They also increased intracellular ROS levels, leading to apoptosis.

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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