Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence

scientific article published on 29 July 2020

Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence is …
instance of (P31):
review articleQ7318358
scholarly articleQ13442814

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P356DOI10.1038/S41392-020-0199-6
P932PMC publication ID7391668
P698PubMed publication ID32728057

P2093author name stringMin Wu
Qiao Wang
Xia Zhao
Hongling Peng
Xiaorong Qi
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Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer.Q34099883
Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upQ34121226
Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2.Q34147360
Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factorsQ34152009
Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.Q34422265
The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesisQ34493341
Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial.Q34520190
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.Q34557699
Growing knowledge of the mTOR signaling networkQ34620724
Deregulation of eIF4E: 4E-BP1 in differentiated human papillomavirus-containing cells leads to high levels of expression of the E7 oncoproteinQ34717857
Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancerQ90857957
Activating human epidermal growth factor receptor 2 (HER2) gene mutation in bone metastases from breast cancerQ90863443
Endocrine therapy in endometrial cancer: An old dog with new tricksQ90927597
Successful maintenance therapy with apatinib inplatinum-resistant advanced ovarian cancer and literature reviewQ90957632
Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trialQ91027526
Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - A randomized phase II trialQ91068249
Phase 1 trial of olaparib and oral cyclophosphamide in BRCA breast cancer, recurrent BRCA ovarian cancer, non-BRCA triple-negative breast cancer, and non-BRCA ovarian cancerQ91100206
Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group studyQ91275584
Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trialQ91465884
Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancerQ91500865
Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 studyQ91694228
Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell CarcinomaQ91700806
Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancerQ91719723
Raf-ERK1/2 signalling pathways mediate steroid hormone synthesis in bovine ovarian granulosa cellsQ91746067
Mechanisms of PARP inhibitor resistance in ovarian cancerQ91799184
Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51Q92051015
Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian CancerQ92086589
Combining PARP inhibition with PD-1 inhibitorsQ92395353
Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trialQ92395369
Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)Q92560472
Pazopanib and Fosbretabulin in recurrent ovarian cancer (PAZOFOS): A multi-centre, phase 1b and open-label, randomised phase 2 trialQ92606752
6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trialQ92614348
Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancerQ92667885
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trialQ92684130
Phase II trial of nintedanib in patients with bevacizumab-resistant recurrent epithelial ovarian, tubal, and peritoneal cancerQ92726174
Antibody-drug conjugates in gynecologic malignanciesQ92726180
Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancersQ92780877
Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid TumorsQ92801272
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 StudyQ92820087
Treatment of recurrent epithelial ovarian cancerQ92847059
Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trialQ92857990
Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trialQ92905904
Molecular markers in uterine serous cancer: Correlation between endometrial biopsy and hysterectomy specimensQ93000430
Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trialQ93043588
The MITO CERV-2 trial: A randomized phase II study of cetuximab plus carboplatin and paclitaxel, in advanced or recurrent cervical cancerQ93063820
Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 TrialQ93121862
Prognostic significance of PD-1 and PD-L1 positive tumor-infiltrating immune cells in ovarian carcinomaQ93160975
Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis.Q34768853
A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.Q34781699
Overexpression of Tumor Vascular Endothelial Growth Factor A May Portend an Increased Likelihood of Progression in a Phase II Trial of Bevacizumab and Erlotinib in Resistant Ovarian CancerQ34781970
Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: a Gynecologic Oncology Group studyQ34850394
Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group studyQ35023418
Expression and significance of CD44, CD47 and c-met in ovarian clear cell carcinomaQ35139055
Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinomaQ35144264
Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix: a Gynecologic Oncology Group studyQ35154219
Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials GroupQ35172203
A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: a gynecologic oncology group studyQ35180428
Src family kinases and paclitaxel sensitivityQ35214722
A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group StudyQ35216723
Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research InstituteQ35602123
Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing PeptibodyQ35604097
Phosphatidylinositol-3-kinase as a therapeutic target in melanomaQ35606261
A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group studyQ35747034
A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group studyQ35748507
Poly (ADP-ribose) polymerase inhibitors: recent advances and future development.Q35895214
Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical updateQ35904534
Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study.Q35913613
A phase I study of tivantinib in combination with temsirolimus in patients with advanced solid tumorsQ49881127
Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trialQ49975220
HER kinase inhibition in patients with HER2- and HER3-mutant cancersQ50115014
Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial.Q50564383
Pazopanib and liposomal doxorubicin in the treatment of patients with relapsed/refractory epithelial ovarian cancer: a phase Ib study of the Sarah Cannon Research Institute.Q50591367
Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial.Q50664932
Phase 2 trial of everolimus and letrozole in relapsed estrogen receptor-positive high-grade ovarian cancers.Q50684803
Relationship between HER2 and JAK/STAT-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer.Q50696151
A phase II study of bevacizumab in combination with definitive radiotherapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma: preliminary results of RTOG 0417.Q50964092
Dual blockade of PI3K/AKT/mTOR (NVP-BEZ235) and Ras/Raf/MEK (AZD6244) pathways synergistically inhibit growth of primary endometrioid endometrial carcinoma cultures, whereas NVP-BEZ235 reduces tumor growth in the corresponding xenograft models.Q50981985
Endometrial Cancers With Activating KRas Mutations Have Activated Estrogen Signaling and Paradoxical Response to MEK Inhibition.Q51006519
A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma.Q51065459
A Combination of Two Receptor Tyrosine Kinase Inhibitors, Canertinib and PHA665752 Compromises Ovarian Cancer Cell Growth in 3D Cell Models.Q51110603
Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study.Q51576159
A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors.Q52611153
A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma.Q52628568
Steroid hormone synthesis by the ovarian stroma surrounding epithelial ovarian tumors: a potential mechanism in ovarian tumorigenesis.Q52763151
The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer.Q52799875
HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation.Q52808198
A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†.Q52839148
Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial.Q52867263
PI3K/AKT pathway-mediated regulation of p27(Kip1) is associated with cell cycle arrest and apoptosis in cervical cancer.Q52955313
Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer.Q53093760
Temsirolimus in women with platinum-refractory/resistant ovarian cancer or advanced/recurrent endometrial carcinoma. A phase II study of the AGO-study group (AGO-GYN8).Q53177591
Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial.Q53668957
A phase II trial of paclitaxel, carboplatin, and bevacizumab in advanced and recurrent endometrial carcinoma (EMCA).Q53673760
Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer.Q54326161
A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor moQ54526385
Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer.Q54566293
A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study.Q54656439
PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression.Q55004657
Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.Q55005815
RAS oncogenes: the first 30 years.Q55036584
Analysis of 1,115 patients tested for MET amplification and therapy response in the MD Anderson Phase I Clinic.Q55070567
Targeting ERBB2 mutations in solid tumors: biological and clinical implications.Q55512723
Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutationQ56240758
A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancerQ56516705
Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian CancerQ56807699
Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trialQ56957787
Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trialQ56967070
Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomisedQ57173042
A randomized phase II/III trial of conventional paclitaxel and carboplatin with or without bevacizumab vs dose-dense paclitaxel and carboplatin with or without bevacizumab, in stage IVB, recurrent or persistent cervical carcinoma: Japan Clinical OncoQ57181489
Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian CancerQ57806929
Antibody Drug Conjugates in the Treatment of Epithelial Ovarian CancerQ58549061
Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trialQ58599459
Antiangiogenic therapy in oncology: current status and future directionsQ38725587
Regulation of epithelial-mesenchymal transition in endometrial cancer: connecting PI3K, estrogen signaling, and microRNAsQ38726364
Long non-coding RNA ANRIL indicates a poor prognosis of cervical cancer and promotes carcinogenesis via PI3K/Akt pathwaysQ38728396
Blocking NOTCH Pathway can Enhance the Effect of EGFR Inhibitor through Targeting CD133+ Endometrial Cancer CellsQ38735642
Ovarian Cancers Harbor Defects in Nonhomologous End Joining Resulting in Resistance to RucaparibQ38742492
Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast CancerQ38743961
Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genesQ38757645
Notch and TGFβ form a positive regulatory loop and regulate EMT in epithelial ovarian cancer cellsQ38778435
Treatment strategies for endometrial cancer: current practice and perspective.Q38784346
α-Ketobenzothiazole Serine Protease Inhibitors of Aberrant HGF/c-MET and MSP/RON Kinase Pathway Signaling in CancerQ38793227
Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 StudyQ38794249
VEGF gene polymorphisms and outcome of epithelial ovarian cancer patientsQ38805626
Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trialQ38822258
Double-Blind, Placebo-Controlled, Randomized Phase III Trial Evaluating Pertuzumab Combined With Chemotherapy for Low Tumor Human Epidermal Growth Factor Receptor 3 mRNA-Expressing Platinum-Resistant Ovarian Cancer (PENELOPE).Q38857412
Antibody-drug conjugates for cancer therapy.Q38864720
Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trialQ38879397
PI3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-α/VEGF pathway in endometrial cancer.Q38882236
IMGN853, a Folate Receptor-α (FRα)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing TumorsQ38883288
A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid TumorsQ38926282
Sonic hedgehog-Gli1 signals promote epithelial-mesenchymal transition in ovarian cancer by mediating PI3K/AKT pathwayQ38937086
Clinical Pharmacokinetics and Pharmacodynamics of Pazopanib: Towards Optimized DosingQ38968504
The role of fulvestrant in endometrial cancerQ38970776
Clinical Pharmacokinetics and Pharmacodynamics of CediranibQ39036230
Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.Q39138428
Tumor angiogenesis and vascular normalization: alternative therapeutic targetsQ39403862
Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group studyQ39499020
Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV.Q39620425
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safetyQ39933788
Involvement of a JAK/STAT pathway inhibitor: cytokine inducible SH2 containing protein in breast cancerQ39979699
Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal JunctionQ39991776
ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor modelsQ40138516
Phase II study of irinotecan in combination with bevacizumab in recurrent ovarian cancer.Q40434632
P275copyright licenseCreative Commons AttributionQ6905323
P433issue1
P921main subjectfemale reproductive system neoplasmQ56014489
P304page(s)137
P577publication date2020-07-29
P1433published inSignal Transduction and Targeted TherapyQ108821959
P1476titleTargeted therapies in gynecological cancers: a comprehensive review of clinical evidence
P478volume5