Effects of olaparib: A Synthesis of Findings from 26 Studies

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Original Abstract of the Article

Major Research Findings

Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has shown effectiveness in treating metastatic triple-negative breast cancer (TNBC) with germline mutations in DNA damage repair (DDR) genes BRCA1/2 (gBRCA-mut). 11 Olaparib enhances the cytotoxicity of various anticancer drugs, making it a potential treatment option for advanced ovarian and breast cancers. 19 Studies have shown that olaparib can be used effectively as a single agent or in combination with other treatments like chemotherapy. 22 Olaparib can potentiate the effects of radiotherapy by inhibiting the release of PARP from radiotherapy-induced damaged DNA, potentially improving treatment outcomes. 20 Olaparib, targeting cellular DNA damage repair pathways, offers a new approach to maximizing the effects of multimodality treatments like radiotherapy. 3 Olaparib has the potential to restore the sensitivity of TNBC cells to chemotherapy in the context of a BRCA1 mutation. 15 Olaparib can enhance the killing effects of etoposide in retinoblastoma cells, which have a loss-of-function mutation in both copies of the RB1 gene. 8 Beyond its anticancer effects, olaparib demonstrates protective effects against oxidative stress in cells and in vivo models. 18 Olaparib has shown promising antitumor effects in certain tumor types, making it a potential therapeutic agent. 12 Olaparib, at clinically relevant concentrations, exerts cytoprotective effects and modulates inflammatory cytokine production without interfering with the ability of cells to phagocytose or eradicate pathogens. 6 Olaparib has demonstrated neuroprotective effects in a mouse model of transient cerebral ischemia. 24

Benefits and Risks

Benefit Summary

Olaparib holds promise as a potential treatment for various cancers. It can be used effectively as a single agent or in combination with other treatments. Olaparib has the potential to enhance the effects of radiotherapy and restore the sensitivity of cancer cells to chemotherapy. Furthermore, olaparib demonstrates protective effects against oxidative stress and may have neuroprotective effects. These benefits make olaparib a potentially valuable therapeutic agent for various cancer types. 22 15 20 12 18 24

Risk Summary

Olaparib may induce cutaneous side effects. 7 Olaparib can interact with other drugs when used in combination. 21 As a PARP inhibitor, olaparib blocks the function of PARP, an enzyme involved in DNA damage repair. This inhibition can lead to an accumulation of DNA damage, potentially promoting cancer cell growth. While olaparib offers protection against oxidative stress, this effect could potentially contribute to the growth of cancer cells. 18

Comparison Between Studies

Similarities in Studies

Many studies have shown that olaparib is a promising therapeutic agent for various cancers. Olaparib can be effective as a single agent or in combination with other treatments. The mechanism of action is often attributed to the inhibition of DNA damage repair, leading to the suppression of cancer cell growth. Overall, olaparib shows potential as a valuable therapeutic agent for diverse cancer types. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Differences in Studies

The effects of olaparib can vary based on the type of cancer and the treatment regimen. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Consistency and Contradictions in the Results

The effects of olaparib can vary based on the type of cancer and the treatment regimen. Olaparib can also lead to side effects in some patients. The safety and efficacy of olaparib require further investigation. More research is needed to better understand the effects of olaparib. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Considerations for Real-World Applications

Olaparib holds promise as a potential treatment for various cancers. However, it is important to understand that olaparib can cause side effects. Consulting with a doctor and understanding the risks and benefits of olaparib are crucial before starting treatment. The safety and efficacy of olaparib require further investigation. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Limitations of Current Research

The effects of olaparib can vary based on the type of cancer and the treatment regimen. Olaparib can also lead to side effects in some patients. The safety and efficacy of olaparib require further investigation. More research is needed to better understand the effects of olaparib. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Future Research Directions

More research is needed to gain a deeper understanding of the effects of olaparib. Specifically, investigating the safety and efficacy of olaparib across various cancer types and treatment regimens is essential. Research into methods to mitigate the side effects of olaparib is also crucial. Olaparib holds promise as a potential treatment for various cancers. Research into olaparib is expected to become increasingly important in the future. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Conclusion

Olaparib holds promise as a potential treatment for various cancers. It can be used effectively as a single agent or in combination with other treatments. The safety and efficacy of olaparib require further investigation. Olaparib is a promising therapeutic agent for various cancers. Research into olaparib is expected to become increasingly important in the future. For more information about olaparib, consult with your doctor. 19 11 3 16 17 23 22 20 5 25 15 8 10 12 6 24 9 13 4 2 1 26

Literature analysis of 26 papers
Positive Content
24
Neutral Content
1
Negative Content
1
Article Type
0
0
0
0
26
2.

Combining Olaparib and Ascorbic Acid on Nanoparticles to Enhance the Drug Toxic Effects in Pancreatic Cancer.

Author: QuiñoneroFrancisco, Parra-TorrejónBelén, Ramírez-RodríguezGloria B, GarcésVictor, Delgado-LópezJosé M, Jiménez-LunaCristina, PerazzoliGloria, MelguizoConsolación, PradosJose, OrtízRaul

Drug resistance reduction
Pancreatic cancer treatment

This study investigated the potential of functionalizing calcium phosphate-based nanoparticles (NPs) with Olaparib (OLA, a PARP-1 inhibitor) and ascorbic acid (AA) to enhance their individual effects against pancreatic cancer (PC) resistance.

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

Language : English

3.

A Mathematical Model to Investigate the Effects of Ceralasertib and Olaparib in Targeting the Cellular DNA Damage Response Pathway.

Author: PughKira, DaviesMichael, PowathilGibin

Cancer cell toxicity enhancement
Synergistic drug activity

This study developed a mathematical model to investigate the effects of ceralasertib and olaparib, two drugs that target DNA damage repair pathways. The model showed that combining these drugs at lower doses for shorter periods could be more effective than using either drug alone.

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.

A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer.

Author: ParaghamianSarah E, QiuJianqing, HawkinsGabrielle M, ZhaoZiyi, SunWenchuan, FanYali, ZhangXin, SuoHongyan, HaoTianran, PrabhuVarun Vijay, AllenJoshua E, ZhouChunxiao, Bae-JumpVictoria

Endometrial cancer treatment

PARP inhibitors are effective for cancers with homologous recombination deficiencies. ONC206, an imipridone, has anti-tumor effects in endometrial cancer by inducing apoptosis and modulating PI3K/AKT signaling. This study found that combining olaparib (a PARP inhibitor) with ONC206 showed synergistic anti-proliferative effects, increased apoptosis, and reduced tumor growth in endometrial cancer cell lines and a mouse model.

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

6.

Effects of the PARP Inhibitor Olaparib on the Response of Human Peripheral Blood Leukocytes to Bacterial Challenge or Oxidative Stress.

Author: SantosSidneia Sousa, BrunialtiMilena Karina Coló, RodriguesLarissa de Oliveira Cavalcanti Peres, LiberatoreAna Maria Alvim, KohIvan Hong Jun, MartinsVanessa, SorianoFrancisco Garcia, SzaboCsaba, SalomãoReinaldo

Cytoprotective effects
Sepsis treatment potential

Olaparib, a PARP1 inhibitor, is clinically used to treat various diseases, including sepsis. This study assessed the effects of olaparib on human peripheral blood leukocytes challenged with bacteria, LPS, or oxidative stress. Olaparib did not negatively impact lymphocyte viability or hinder pathogen eradication, but it exerted cytoprotective effects and modulated inflammatory cytokine production. The findings suggest olaparib may be a potential experimental therapy for septic shock.

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

7.

Olaparib-induced cutaneous side effects in a patient with recurrent ovarian cancer.

Author: GouRei, HorikawaNaoki, KosakaKenzo

BRCA mutation treatment
Ovarian cancer treatment
Dermatosis
Quality of life impact

PARP inhibitors are a new class of drugs used to treat ovarian cancer, especially in patients with BRCA gene mutations. This study reports a rare side effect of olaparib, a PARP inhibitor, which caused a skin rash on the hand.

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

11.

Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial.

Author: SchettiniFrancesco, CoronaSilvia Paola, GiudiciFabiola, StrinaCarla, SiricoMarianna, BernocchiOttavia, MilaniManuela, ZiglioliNicoletta, AgugginiSergio, AzziniCarlo, BarbieriGiuseppina, CervoniValeria, CappellettiMaria Rosa, MolteniAlfredo, LazzariMaria Chiara, FerreroGiuseppina, UngariMarco, MarascoElena, BrusonAlice, XumerleLuciano, ZagoElisa, CerraDavide, LoddoMarco, WilliamsGareth H, ParisIda, ScambiaGiovanni, GeneraliDaniele

Olaparib for TNBC

This study aimed to identify potential biomarkers for early response to olaparib in triple-negative breast cancer (TNBC). The OLTRE trial explored various pathologic, radiometabolic, and immune markers in both BRCA-wild type and BRCA-mutant TNBC. The study provides preliminary insights into potential biomarkers for predicting olaparib efficacy in different TNBC subtypes.

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

Language : English

12.

ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer.

Author: NamAh-Rong, YoonJeesun, JinMei-Hua, BangJu-Hee, OhKyoung-Seok, SeoHye-Rim, KimJae-Min, KimTae-Yong, OhDo-Youn

Biliary tract cancer treatment
None mentioned

Combining olaparib, a PARP inhibitor, with an ATR inhibitor like ceralasertib may be a promising treatment for biliary tract cancer, showing synergistic anti-proliferative effects and tumor suppression in preclinical models.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health 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

13.

Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.

Author: GuptaVijayalaxmi G, HirstJeff, PetersenShariska, RobyKatherine F, KuschMeghan, ZhouHelen, CliveMakena L, JewellAndrea, PathakHarsh B, GodwinAndrew K, WilsonAndrew J, CrispensMarta A, CybullaEmily, VindigniAlessandro, FuhKatherine C, KhabeleDineo

Treat HR-proficient cancer

PARPi inhibitors are effective against ovarian tumors with BRCA1/2 mutations, but other subtypes, including those with CCNE1 amplification, require alternative treatments. This study provides preclinical evidence supporting a clinical trial investigating the combination of olaparib (a PARPi) and entinostat (a histone deacetylase inhibitor) for recurrent HR-proficient ovarian cancer.

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

14.

Synergistic effects of olaparib combined with <i>ERCC1</i> on the sensitivity of cisplatin in non-small cell lung cancer.

Author: XieKejie, NiXiaoyan, LvShanmei, ZhouGuozhong, HeHonger

NSCLC treatment

This study investigated the synergistic effects of the PARP inhibitor olaparib combined with ERCC1 expression on the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin.

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

Language : English

17.

Effects of the Poly(ADP-Ribose) Polymerase Inhibitor Olaparib in Cerulein-Induced Pancreatitis.

Author: AhmadAkbar, Haas De MelloAline, SzczesnyBartosz, TöröGábor, MarcattiMichela, DruzhynaNadiya, LiaudetLucas, TarantiniStefano, SalomaoReinaldo, Garcia SorianoFrancisco, SzaboCsaba

Pancreatitis treatment

This study investigates the efficacy and safety of olaparib, a PARP inhibitor, in an experimental model of pancreatitis. Olaparib showed potential therapeutic benefit in both in vivo and in vitro models, suggesting a possible role in managing pancreatitis.

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

18.

The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis.

Author: AhmadAkbar, VieiraJuliana de Camargo, de MelloAline Haas, de LimaThais Martins, ArigaSuely Kubo, BarbeiroDenise Frediani, BarbeiroHermes Vieira, SzczesnyBartosz, TöröGábor, DruzhynaNadiya, RandiElisa B, MarcattiMichela, Toliver-KinskyTracy, KissAndrás, LiaudetLucas, SalomaoReinaldo, SorianoFrancisco Garcia, SzaboCsaba

Extended survival
Improved bioenergetics
Improved organ function
Reduced inflammation
Age related effects
None observed
Sex specific effects

This study investigates the efficacy and safety of olaparib, a PARP inhibitor, in experimental models of oxidative stress and sepsis. Olaparib improved multiorgan dysfunction, reduced bacterial CFUs, and extended survival in male mice subjected to CLP. It also modulated miRNA expression and immune cell populations. The findings suggest that olaparib may be repurposed for the treatment of septic shock.

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

19.

Synergistic Effects of Olaparib and DNA-damaging Agents in Oesophageal Squamous Cell Carcinoma Cell Lines.

Author: MiyamotoKeisuke, MinegakiTetsuya, TanahashiMami, YamamotoAyaka, MoriyamaYumi, WadaAkari, MatsumotoAyaka, OtaKeisuke, TanakaMai, MasudaUtako, TsujimotoMasayuki, NishiguchiKohshi

ESCC treatment

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, enhances the cytotoxicity of various anticancer drugs. This study examined the effect of olaparib on the cytotoxicity of anticancer drugs in esophageal squamous cell carcinoma (ESCC) cell lines, suggesting that olaparib may be a potential secondary treatment option for ESCC.

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

Language : English

21.

Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours.

Author: PlummerRuth, VerheulHenk M, De VosFilip Y F L, LeunenKarin, MolifeL Rhoda, RolfoChristian, Grundtvig-SørensenPeter, De GrèveJacques, RotteySylvie, JerusalemGuy, ItalianoAntoine, SpicerJames, DirixLuc, GoesslCarsten, BirkettJoseph, SpencerStuart, LearoydMaria, BaileyChristopher, DeanEmma

Breast cancer treatment

This phase I study investigated the safety and pharmacokinetic profiles of olaparib, a PARP inhibitor, in combination with different endocrine therapies (tamoxifen, anastrozole, or letrozole) for treating patients with advanced solid tumors. The study aimed to assess the safety and drug levels in the body when these medications were combined.

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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

25.

Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells.

Author: MinAhrum, ImSeock-Ah, KimDebora Keunyoung, SongSang-Hyun, KimHee-Jun, LeeKyung-Hun, KimTae-Yong, HanSae-Won, OhDo-Youn, KimTae-You, O'ConnorMark J, BangYung-Jue

DNA repair inhibition
cancer treatment

The study explored the potential for HDAC inhibition to enhance the anti-tumor effect of PARP inhibitors.

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

26.

Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines.

Author: PierceAisling, McGowanPatricia M, CotterMaura, MulloolyMaeve, O'DonovanNorma, RaniSweta, O'DriscollLorraine, CrownJohn, DuffyMichael J

Olaparib and CDK1 inhibitor
Olaparib and pan HER inhibitor
Olaparib for breast cancer

This study compared the antiproliferative activity of olaparib and iniparib, two PARP inhibitors, in a panel of breast cancer cell lines. Olaparib was a more potent inhibitor of cell growth than iniparib in most cell lines. Combining olaparib with a CDK1 inhibitor or a pan HER inhibitor resulted in superior growth inhibition.

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

Language : English

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