Harnessing the value of TCTP in breast cancer treatment resistance: an opportunity for personalized therapy

Gianluca Santamaria , Mario Cioce , Antonia Rizzuto , Vito Michele Fazio , Giuseppe Viglietto , Maria Lucibello

Cancer Drug Resistance ›› 2023, Vol. 6 ›› Issue (3) : 447 -67.

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Cancer Drug Resistance ›› 2023, Vol. 6 ›› Issue (3) :447 -67. DOI: 10.20517/cdr.2023.21
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Harnessing the value of TCTP in breast cancer treatment resistance: an opportunity for personalized therapy

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Abstract

Early identification of breast cancer (BC) patients at a high risk of progression may aid in therapeutic and prognostic aims. This is especially true for metastatic disease, which is responsible for most cancer-related deaths. Growing evidence indicates that the translationally controlled tumor protein (TCTP) may be a clinically relevant marker for identifying poorly differentiated aggressive BC tumors. TCTP is an intriguing protein with pleiotropic functions, which is involved in multiple signaling pathways. TCTP may also be involved in stress response, cell growth and proliferation-related processes, underlying its potential role in the initiation of metastatic growth. Thus, TCTP marks specific cancer cell sub-populations with pronounced stress adaptation, stem-like and immune-evasive properties. Therefore, we have shown that in vivo phospho-TCTP levels correlate with the response of BC cells to anti-HER2 agents. In this review, we discuss the clinical relevance of TCTP for personalized therapy, specific TCTP-targeting strategies, and currently available therapeutic agents. We propose TCTP as an actionable clinically relevant target that could potentially improve patient outcomes.

Keywords

Breast cancer / metastasis / TCTP / stem cells / therapy resistance / biomarker

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Gianluca Santamaria, Mario Cioce, Antonia Rizzuto, Vito Michele Fazio, Giuseppe Viglietto, Maria Lucibello. Harnessing the value of TCTP in breast cancer treatment resistance: an opportunity for personalized therapy. Cancer Drug Resistance, 2023, 6(3): 447-67 DOI:10.20517/cdr.2023.21

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References

[1]

El-deiry WS,Lenz H.The current state of molecular testing in the treatment of patients with solid tumors, 2019.CA Cancer J Clin2019;69:305-43 PMCID:PMC6767457

[2]

Latha NR,Nadhan R.Gene expression signatures: a tool for analysis of breast cancer prognosis and therapy.Crit Rev Oncol Hematol2020;151:102964

[3]

Garufi G,Arcanà C.Tailoring neoadjuvant treatment of HR-positive/HER2-negative breast cancers: which role for gene expression assays?.Cancer Treat Rev2022;110:102454

[4]

Vallon-christersson J,Hegardt C.Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series.Sci Rep2019;9:12184 PMCID:PMC6704148

[5]

Doll S,Mann M.The case for proteomics and phospho-proteomics in personalized cancer medicine.Prot Clin Appl2019;13:1800113 PMCID:PMC6519247

[6]

Liu Y,Aebersold R.On the dependency of cellular protein levels on mRNA abundance.Cell2016;165:535-50

[7]

Cioce M,Donzelli S.Breast cancer metastasis: is it a matter of OMICS and proper ex-vivo models?.Comput Struct Biotechnol J2022;20:4003-8 PMCID:PMC9355905

[8]

Dahlgren M,Brueffer C.Preexisting somatic mutations of estrogen receptor alpha (ESR1) in early-stage primary breast cancer.JNCI Cancer Spectr2021;5:pkab028 PMCID:PMC8060794

[9]

Macdonald SM,Jabs EW.Chromosomal localization of tumor protein, translationally-controlled 1 (TPT1) encoding the human histamine releasing factor (HRF) to13q12→q14.Cytogenet Cell Genet1999;84:128-9

[10]

Bommer U.Dysregulation of TCTP in biological processes and diseases.Cells2020;9:1632 PMCID:PMC7407922

[11]

Consortium. Uniprot: the universal protein knowledgebase in 2023.Nucleic Acids Res2023;51:D523-31 PMCID:PMC9825514

[12]

Susini L,Duflaut D.TCTP protects from apoptotic cell death by antagonizing bax function.Cell Death Differ2008;15:1211-20

[13]

Thaw P,Hounslow AM,Waltho JP.Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones.Nat Struct Biol2001;8:701-4

[14]

Dong X,Li Y,Ding J.Molecular basis of the acceleration of the GDP-GTP exchange of human ras homolog enriched in brain by human translationally controlled tumor protein.J Biol Chem2009;284:23754-64 PMCID:PMC2749149

[15]

Bommer U.Role of TCTP in cell biological and disease processes.Cells2021;10:2290 PMCID:PMC8471051

[16]

Yağcı M,Akyürek N.TCTP/HRF pathway and angiogenesis: a feasible intercourse in chronic lymphocytic leukemia.Leuk Res2013;37:665-70

[17]

Børset M,Vandsemb EN.Highly expressed genes in multiple myeloma cells - what can they tell us about the disease?.Eur J Haematol2022;109:31-40 PMCID:PMC9310595

[18]

Amson R,Lespagnol A.Reciprocal repression between P53 and TCTP.Nat Med2012;18:91-9

[19]

Lucibello M,Antelmi E.Phospho-TCTP as a therapeutic target of dihydroartemisinin for aggressive breast cancer cells.Oncotarget2015;6:5275-91 PMCID:PMC4467148

[20]

Chen C,Hua M.Expression and clinical role of TCTP in epithelial ovarian cancer.J Mol Histol2015;46:145-56

[21]

Zhu X,Xu D.Upregulation of translationally controlled tumor protein is associated with cervical cancer progression.Front Mol Biosci2021;8:686718 PMCID:PMC8473787

[22]

Zhang F,Xu Z.Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer.J Exp Clin Cancer Res2017;36:68 PMCID:PMC5433060

[23]

Zhang F,Wang Z.A novel regulatory mechanism of Pim-3 kinase stability and its involvement in pancreatic cancer progression.Mol Cancer Res2013;11:1508-20

[24]

Miao X,Xu SL.TCTP overexpression is associated with the development and progression of glioma.Tumour Biol2013;34:3357-61

[25]

Gu X,Ma G.TCTP promotes glioma cell proliferation in vitro and in vivo via enhanced β-catenin/TCF-4 transcription.Neuro Oncol2014;16:217-27 PMCID:PMC3895383

[26]

Slaby O,Svoboda M.Significant overexpression of Hsp110 gene during colorectal cancer progression.Oncol Rep2009;21:1235-41

[27]

Xiao B,Luo S.Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/ MMP9 signaling.Oncotarget2016;7:50057-73 PMCID:PMC5226568

[28]

Baylot V,Andrieu C.Targeting TCTP as a new therapeutic strategy in castration-resistant prostate cancer.Mol Ther2012;20:2244-56 PMCID:PMC3519986

[29]

Rocca BJ,Barone A.Translationally controlled tumor protein in prostatic adenocarcinoma: correlation with tumor grading and treatment-related changes.Biomed Res Int2015;2015:985950 PMCID:PMC4312572

[30]

Sun R,Gong L.TCTP promotes epithelial-mesenchymal transition in lung adenocarcinoma.Onco Targets Ther2019;12:1641-53 PMCID:PMC6398409

[31]

Liu LZ,Xin Q,Chen GG.The permissive role of TCTP in PM2.5/NNK-induced epithelial-mesenchymal transition in lung cells.J Transl Med2020;18:66 PMCID:PMC7011287

[32]

Phanthaphol N,Loilome W.Upregulation of TCTP is associated with cholangiocarcinoma progression and metastasis.Oncol Lett2017;14:5973-9 PMCID:PMC5661414

[33]

Kobayashi D,Komohara Y.Translationally controlled tumor protein is a novel biological target for neurofibromatosis type 1-associated tumors.J Biol Chem2014;289:26314-26 PMCID:PMC4176225

[34]

Ramani P,Sowa-Avugrah E.High levels of polo-like kinase 1 and phosphorylated translationally controlled tumor protein indicate poor prognosis in neuroblastomas.J Neurooncol2015;125:103-11

[35]

Pece S,Confalonieri S.Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content.Cell2010;140:62-73

[36]

Santoro A,Luzi L.p53 Loss in breast cancer leads to myc activation, increased cell plasticity, and expression of a mitotic signature with prognostic value.Cell Rep2019;26:624-38.e8 PMCID:PMC6334229

[37]

Yucer N,Workman MJ.Human iPSC-derived fallopian tube organoids with BRCA1 mutation recapitulate early-stage carcinogenesis.Cell Rep2021;37:110146 PMCID:PMC9000920

[38]

Rae C,Braconi C.Patient-derived organoids as a model for cancer drug discovery.Int J Mol Sci2021;22:3483 PMCID:PMC8038043

[39]

Yarm FR.Plk phosphorylation regulates the microtubule-stabilizing protein TCTP.Mol Cell Biol2002;22:6209-21 PMCID:PMC134017

[40]

Cucchi U,De Ponti A.Phosphorylation of TCTP as a marker for polo-like kinase-1 activity in vivo.Anticancer Res2010;30:4973-85Available from: https://pubmed.ncbi.nlm.nih.gov/21187478/. [Last accessed on 12 Jul 2023]

[41]

Lemmens B,Akopyan K.DNA replication determines timing of mitosis by restricting CDK1 and PLK1 activation.Mol Cell2018;71:117-28.e3 PMCID:PMC6039720

[42]

Malard F,Alami M,Lescop E.Conformational ensemble and biological role of the TCTP intrinsically disordered region: influence of calcium and phosphorylation.J Mol Biol2018;430:1621-39

[43]

Combes G,Braga LG.Playing polo during mitosis: PLK1 takes the lead.Oncogene2017;36:4819-27

[44]

Rizki A,Bissell MJ.Polo-like kinase 1 is involved in invasion through extracellular matrix.Cancer Res2007;67:11106-10 PMCID:PMC3730820

[45]

King SI,Bray SE.Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast cancer is associated with TP53 mutation and poor clinical outcom.Breast Cancer Res2012;14:R40 PMCID:PMC3446374

[46]

Montaudon E,Sourd L.PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance.Nat Commun2020;11:4053 PMCID:PMC7426966

[47]

Bhola NE,Bafna S.Kinome-wide functional screen identifies role of PLK1 in hormone-independent, ER-positive breast cancer.Cancer Res2015;75:405-14 PMCID:PMC4297507

[48]

Donizy P,Surowiak P,Kozyra C.Augmented expression of Polo-like kinase 1 is a strong predictor of shorter cancer-specific overall survival in early stage breast cancer at 15-year follow-up.Oncol Lett2016;12:1667-74 PMCID:PMC4998224

[49]

D’Amico S,Manni I.DHA affects microtubule dynamics through reduction of phospho-TCTP levels and enhances the antiproliferative effect of T-DM1 in trastuzumab-resistant HER2-positive breast cancer cell lines.Cells2020;9:1260 PMCID:PMC7290969

[50]

Gioia D, Stieber P, Schmidt GP, Nagel D, Heinemann V, Baur-Melnyk A. Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase.Br J Cancer2015;112:809-18 PMCID:PMC4453962

[51]

Kawakami Y,Kawakami T.Histamine-releasing factor, a new therapeutic target in allergic diseases.Cells2019;8:1515 PMCID:PMC6952944

[52]

Kim M,Lee H.Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis.Exp Mol Med2021;53:67-80 PMCID:PMC8080778

[53]

Zhang L,Karlan S.Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer.PLoS One2010;5:e15573 PMCID:PMC3013113

[54]

Kim JE,Kim YH,Park YG.Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model.Exp Mol Med2008;40:709-20 PMCID:PMC2679342

[55]

Freitas AJA,Varuzza MB.Liquid biopsy as a tool for the diagnosis, treatment, and monitoring of breast cancer.Int J Mol Sci2022;23:9952 PMCID:PMC9456236

[56]

Amzallag N,Allanic D.TSAP6 facilitates the secretion of translationally controlled tumor protein/histamine-releasing factor via a nonclassical pathway.J Biol Chem2004;279:46104-12

[57]

Chen M,Ji H.Transcriptome and long noncoding RNA sequencing of three extracellular vesicle subtypes released from the human colon cancer LIM1863 cell line.Sci Rep2016;6:38397 PMCID:PMC5137021

[58]

Ferrer E,Hassan D.A potential role for exosomal translationally controlled tumor protein export in vascular remodeling in pulmonary arterial hypertension.Am J Respir Cell Mol Biol2018;59:467-78 PMCID:PMC6178156

[59]

Kumar V,Tcyganov E.The nature of myeloid-derived suppressor cells in the tumor microenvironment.Trends Immunol2016;37:208-20 PMCID:PMC4775398

[60]

Wu Y,Niu M,Wu K.Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy.Mol Cancer2022;21:184 PMCID:PMC9513992

[61]

Hangai S,Kimura Y.Orchestration of myeloid-derived suppressor cells in the tumor microenvironment by ubiquitous cellular protein TCTP released by tumor cells.Nat Immunol2021;22:947-57

[62]

Sangaletti S,Santangelo A.Mesenchymal transition of high-grade breast carcinomas depends on extracellular matrix control of myeloid suppressor cell activity.Cell Rep2016;17:233-48

[63]

Chen X,Huang Y,Xie N.Mechanisms and strategies to overcome PD-1/PD-L1 blockade resistance in triple-negative breast cancer.Cancers2022;15:104 PMCID:PMC9817764

[64]

Sharma P,Wargo JA.Primary, adaptive, and acquired resistance to cancer immunotherapy.Cell2017;168:707-23 PMCID:PMC5391692

[65]

Lee HJ,Oh SJ.Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes.Nat Commun2022;13:2127 PMCID:PMC9019109

[66]

Dongre A.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer.Nat Rev Mol Cell Biol2019;20:69-84

[67]

Yang J,Berx G.EMT International Association (TEMTIA)Guidelines and definitions for research on epithelial-mesenchymal transition.Nat Rev Mol Cell Biol2020;21:341-52 PMCID:PMC7250738

[68]

Massagué J.Metastasis-initiating cells and ecosystems.Cancer Discov2021;11:971-94 PMCID:PMC8030695

[69]

Pastushenko I.EMT transition states during tumor progression and metastasis.Trends Cell Biol2019;29:212-26

[70]

Lee MY.Embryonic programs in cancer and metastasis-insights from the mammary gland.Front Cell Dev Biol2022;10:938625 PMCID:PMC9277484

[71]

Chen SH,Chou CH.A knockout mouse approach reveals that TCTP functions as an essential factor for cell proliferation and survival in a tissue- or cell type-specific manner.Mol Biol Cell2007;18:2525-32 PMCID:PMC1924818

[72]

Hsu YC,Cai Y,Choi KW.Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase.Nature2007;445:785-8

[73]

Kwon YV,Xu C.The role of translationally controlled tumor protein in proliferation of Drosophila intestinal stem cells.Proc Natl Acad Sci U S A2019;116:26591-8 PMCID:PMC6936429

[74]

Zhang Q,Shi L.miR-145-5p inhibits the proliferation of glioma stem cells by targeting translationally controlled tumor protein.J Cancer2022;13:1490-500 PMCID:PMC8965115

[75]

Bae SY,Lee KJ.Translationally controlled tumor protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis.Sci Rep2015;5:8061 PMCID:PMC4306963

[76]

Mishra DK,Sharma A.Translationally controlled tumor protein (TCTP) is required for TGF-β1 induced epithelial to mesenchymal transition and influences cytoskeletal reorganization.Biochim Biophys Acta Mol Cell Res2018;1865:67-75

[77]

Bazile F,Arnal I,Chesnel F.Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells.Carcinogenesis2009;30:555-65 PMCID:PMC2831045

[78]

Lucibello M,Zonfrillo M.TCTP is a critical survival factor that protects cancer cells from oxidative stress-induced cell-death.Exp Cell Res2011;317:2479-89

[79]

Bommer UA,Puri P.Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin.Cell Commun Signal2017;15:9 PMCID:PMC5286767

[80]

Jeong M,Kim JE.TCTP protein degradation by targeting mTORC1 and signaling through S6K, Akt, and Plk1 sensitizes lung cancer cells to DNA-damaging drugs.Sci Rep2021;11:20812 PMCID:PMC8531033

[81]

Jung J,Lee YS.Radiosensitivity of cancer cells is regulated by translationally controlled tumor protein.Cancers2019;11:386 PMCID:PMC6468585

[82]

Sinha P,Fischer J.Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis.Electrophoresis2000;21:3048-57

[83]

Peng Y,Zhou C,Zeng C.PI3K/Akt/mTOR pathway and its role in cancer therapeutics: are we making headway?.Front Oncol2022;12:819128 PMCID:PMC8987494

[84]

Vora P,Salim SK.The rational development of CD133-targeting immunotherapies for glioblastoma.Cell Stem Cell2020;26:832-44.e6

[85]

Sambasivan S.Epithelial ovarian cancer: review article.Cancer Treat Res Commun2022;33:100629

[86]

Yang W,Kim DK,Suh DS.Therapeutic strategies for targeting ovarian cancer stem cells.Int J Mol Sci2021;22:5059 PMCID:PMC8151268

[87]

Slack FJ.The role of non-coding RNAs in oncology.Cell2019;179:1033-55 PMCID:PMC7347159

[88]

Zhang P,Chen Q.Non-coding RNAs and their integrated networks.J Integr Bioinform2019;16:20190027 PMCID:PMC6798851

[89]

Li Y,Sun Z.A review of literature: role of long noncoding RNA TPT1-AS1 in human diseases.Clin Transl Oncol2023;25:306-15

[90]

Hu C,Zhang X,Li L.Dyregulation of the lncRNA TPT1-AS1 positively regulates QKI expression and predicts a poor prognosis for patients with breast cancer.Pathol Res Pract2020;216:153216

[91]

Huang Y,Shao X,Li G.Long non-coding RNA TPT1-AS1 sensitizes breast cancer cell to paclitaxel and inhibits cell proliferation by miR-3156-5p/caspase 2 axis.Hum Cell2021;34:1244-54

[92]

Elango R,Shaath H.Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition.Cancer Cell Int2021;21:515 PMCID:PMC8474815

[93]

Wu W,Li X.LncRNA TPT1-AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression.Cancer Sci2019;110:1587-98 PMCID:PMC6500995

[94]

Efferth T.From ancient herb to modern drug: artemisia annua and artemisinin for cancer therapy.Semin Cancer Biol2017;46:65-83

[95]

Yu R,Fujimoto M.Dihydroartemisinin: a potential drug for the treatment of malignancies and inflammatory diseases.Front Oncol2021;11:722331 PMCID:PMC8529146

[96]

Ericsson T,von Hagens C,Äbelö A.Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer.Eur J Clin Pharmacol2014;70:1453-63

[97]

von Hagens C,Goeckenjan M.Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).Breast Cancer Res Treat2017;164:359-69

[98]

Deeken JF,Hartley M.A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies.Cancer Chemother Pharmacol2018;81:587-96

[99]

Efferth T.Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy.Drug Resist Updat2005;8:85-97

[100]

Bhisutthibhan J,Hossler PA.The plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin.J Biol Chem1998;273:16192-8

[101]

Fujita T,Pinkaew D,Liu Z.Human fortilin is a molecular target of dihydroartemisinin.FEBS Lett2008;582:1055-60 PMCID:PMC2727609

[102]

Denkert C,Fasching PA.Biomarker data from the phase III KATHERINE study of adjuvant T-DM1 versus trastuzumab for residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer.Clin Cancer Res2023;29:1569-81 PMCID:PMC10102844

[103]

Tarantino P,Schmid P.Immunotherapy for early triple negative breast cancer: research agenda for the next decade.NPJ Breast Cancer2022;8:23 PMCID:PMC8857212

[104]

Duarte D.Antidepressant drug sertraline against human cancer cells.Biomolecules2022;12:1513 PMCID:PMC9599050

[105]

Tuynder M,Prieur S.Translationally controlled tumor protein is a target of tumor reversion.Proc Natl Acad Sci U S A2004;101:15364-9 PMCID:PMC523462

[106]

Boia-Ferreira M,Hamasaki AE.TCTP as a therapeutic target in melanoma treatment.Br J Cancer2017;117:656-65 PMCID:PMC5572181

[107]

Chinnapaka S,Munirathinam G.Repurposing antidepressant sertraline as a pharmacological drug to target prostate cancer stem cells: dual activation of apoptosis and autophagy signaling by deregulating redox balance.Am J Cancer Res2020;10:2043-65Available from: https://pubmed.ncbi.nlm.nih.gov/32775000/. [Last accessed on 12 Jul 2023] PMCID:PMC7407340

[108]

Li Y,Zhang C.Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics.Oncogene2017;36:6839-49 PMCID:PMC5735297

[109]

Malard F,Nhiri N.Revisiting the molecular interactions between the tumor protein TCTP and the drugs sertraline/thioridazine.ChemMedChem2022;17:e202100528

[110]

Cerma K,Moscetti L.Targeting PI3K/AKT/mTOR pathway in breast cancer: from biology to clinical challenges.Biomedicines2023;11:109 PMCID:PMC9855880

[111]

Frappaolo A,Cesare G.GOLPH3 protein controls organ growth by interacting with TOR signaling proteins in Drosophila.Cell Death Dis2022;13:1003 PMCID:PMC9701223

[112]

Le TP,Kim AR,Choi KW.14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila.Nat Commun2016;7:11501 PMCID:PMC4859069

[113]

Bommer UA,Chen J,Engel M.Growth-factor dependent expression of the translationally controlled tumour protein TCTP is regulated through the PI3-K/Akt/mTORC1 signalling pathway.Cell Signal2015;27:1557-68

[114]

Piccart M,Campone M.Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†.Ann Oncol2014;25:2357-62 PMCID:PMC6267855

[115]

R Core Team (2022). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria..Available from: https://www.R-project.org/. [Last accessed on 12 Jul 2023]

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