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Article ; Online: Combining precision medicine and prophylaxis in oesophageal squamous cell carcinoma.

Baxter, Mark A / Spender, Lindsay C / Petty, Russell D

2020 Volume 123, Issue 11, Page(s) 1585–1587

Abstract: A trial update confirms improved survival for prophylactic elective nodal irradiation and addition of erlotinib to definitive chemoradiotherapy in oesophageal squamous cell carcinoma (ESCC). High tumour EGFR protein expression shows promise to identify ... ...

Abstract	A trial update confirms improved survival for prophylactic elective nodal irradiation and addition of erlotinib to definitive chemoradiotherapy in oesophageal squamous cell carcinoma (ESCC). High tumour EGFR protein expression shows promise to identify those who will benefit from erlotinib. This represents therapeutic progress, and has wider relevance for precision medicine strategies in ESCC.
MeSH term(s)	Carcinoma, Squamous Cell/drug therapy ; Chemoradiotherapy ; Erlotinib Hydrochloride/therapeutic use ; Esophageal Neoplasms/drug therapy ; Esophageal Squamous Cell Carcinoma/therapy ; Head and Neck Neoplasms ; Humans ; Precision Medicine
Chemical Substances	Erlotinib Hydrochloride (DA87705X9K)
Language	English
Publishing date	2020-09-22
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-020-01057-3
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Article ; Online: Targeting BRAF-mutant tumours with TGFBR1 inhibitors.

Spender, Lindsay C / Inman, Gareth J

Aging

2017 Volume 9, Issue 1, Page(s) 5–6

MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Humans ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Protein Kinase Inhibitors/pharmacology ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Receptors, Transforming Growth Factor beta ; TGF-beta type I receptor (EC 2.7.1.11) ; BRAF protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2017-02-01
Publishing country	United States
Document type	Editorial
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.101169
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Article: Female Sex but Not Oestrogen Receptor Expression Predicts Survival in Advanced Gastroesophageal Adenocarcinoma-A Post-hoc Analysis of the GO2 Trial.

Baxter, Mark A / Spender, Lindsay C / Walsh, Shaun / Bray, Susan / Skinner, Gemma / King, Sharon / Hall, Peter S / Seymour, Matthew J / Petty, Russell D / On Behalf Of The Go Investigators

Cancers

2023 Volume 15, Issue 9

Abstract: Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors ...

Abstract	Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and β. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52-90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERβ expression. There was no survival impact according to ERβ expression level. Female sex and younger age were associated with lower ERβ expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age.
Language	English
Publishing date	2023-05-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15092591
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Article: Developments in Burkitt's lymphoma: novel cooperations in oncogenic MYC signaling.

Spender, Lindsay C / Inman, Gareth J

Cancer management and research

2014 Volume 6, Page(s) 27–38

Abstract: ... identifiable by translocation of the c-MYC gene into the immunoglobulin gene loci, resulting in deregulation ... signaling pathways, and members of the B-cell lymphoma-2 family of apoptosis regulators in determining the fate of c ... to synergistically induced BL apoptosis have been proposed. Now, engineering both constitutive c-MYC expression and ...

Abstract	Burkitt's lymphoma (BL) is an aggressive disorder associated with extremely high rates of cell proliferation tempered by high levels of apoptosis. Despite the high levels of cell death, the net effect is one of rapid tumor growth. The tumor arises within the germinal centers of secondary lymphoid tissues and is identifiable by translocation of the c-MYC gene into the immunoglobulin gene loci, resulting in deregulation of the proto-oncogene. Many of the major players involved in determining the development of BL have been characterized in human BL cell lines or in mouse models of MYC-driven lymphomagenesis. Both systems have been useful so far in characterizing the role of tumor suppressor genes (for example, p53), prosurvival signaling pathways, and members of the B-cell lymphoma-2 family of apoptosis regulators in determining the fate of c-MYC overexpressing B-cells, and ultimately in regulating lymphoma development. Signaling through phosphoinositide (PI)3-kinase stands out as being critical for BL cell survival. Recurrent mutations in ID3 or TCF3 (E2A) that promote signaling through PI3-kinase have recently been identified in human BL samples, and new therapeutic strategies based on coordinately targeting both the prosurvival factor, B-cell lymphoma-XL, and the PI3-kinase/AKT/mammalian target of rapamycin (mTOR) signaling pathway to synergistically induced BL apoptosis have been proposed. Now, engineering both constitutive c-MYC expression and PI3-kinase activity, specifically in murine B-cells undergoing the germinal center reaction, has revealed that there is synergistic cooperation between c-MYC and PI3-kinase during BL development. The resulting tumors phenocopy the human malignancy, and acquire tertiary mutations also present in human tumors. This model may, therefore, prove useful in further studies to identify functionally relevant mutational events necessary for BL pathogenesis. This review discusses these cooperating interactions, the possible influence of BL tumor-associated viruses, and highlights potential new opportunities for therapeutic intervention.
Language	English
Publishing date	2014-01-09
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2508013-1
ISSN	1179-1322
ISSN	1179-1322
DOI	10.2147/CMAR.S37745
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Article ; Online: Phosphoinositide 3-kinase/AKT/mTORC1/2 signaling determines sensitivity of Burkitt's lymphoma cells to BH3 mimetics.

Spender, Lindsay C / Inman, Gareth J

Molecular cancer research : MCR

2012 Volume 10, Issue 3, Page(s) 347–359

Abstract: Burkitt's lymphoma (BL), driven by translocation and overexpression of the c-MYC gene, is ... ratios and loss of c-MYC expression. Furthermore, blocking c-MYC function using the inhibitor 10058-F4 ... family members and/or c-MYC by the PI3K/AKT/mTOR pathway could contribute to BL cell survival and ...

Abstract	Burkitt's lymphoma (BL), driven by translocation and overexpression of the c-MYC gene, is an aggressive, highly proliferative lymphoma, and novel therapeutic strategies are required to overcome drug resistance following conventional treatments. The importance of the prosurvival BCL-2 family member BCL-X(L) in BL cell survival suggests that antagonistic BH3-mimetic compounds may have therapeutic potential. Here, we show that treatment of BL cell lines with ABT-737 induces caspase-3/7 activation and apoptosis with varying potency. Using selective inhibitors, we identify phosphoinositide 3-kinase (PI3K) as a proproliferative/survival pathway in BL cells and investigate the potential of combined pharmacologic inhibition of both the BCL-2 family and PI3K signaling pathway. PI3K/AKT inhibition and ABT-737 treatment induced synergistic caspase activation, augmented BL cell apoptosis, and rendered chemoresistant cells sensitive. Targeting mTORC1/2 with PP242 was also effective, either as a monotherapy or, more generally, in combination with ABT-737. The combined use of a dual specificity PI3K/mTOR inhibitor (PI 103) with ABT-737 proved highly efficacious. PI 103 treatment of BL cells was associated with an increase in BIM/MCL-1 expression ratios and loss of c-MYC expression. Furthermore, blocking c-MYC function using the inhibitor 10058-F4 also induced apoptosis synergistically with ABT-737, suggesting that maintenance of expression of BCL-2 family members and/or c-MYC by the PI3K/AKT/mTOR pathway could contribute to BL cell survival and resistance to ABT-737. The combined use of BH3 mimetics and selective mTORC1/2 inhibitors may therefore be a useful novel therapeutic approach for the treatment of B-cell malignancy, including chemoresistant lymphomas.
MeSH term(s)	Apoptosis/drug effects ; Biphenyl Compounds/pharmacology ; Burkitt Lymphoma/enzymology ; Burkitt Lymphoma/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Screening Assays, Antitumor ; Drug Synergism ; Furans/pharmacology ; Humans ; Indoles/pharmacology ; Mechanistic Target of Rapamycin Complex 1 ; Multiprotein Complexes ; Nitrophenols/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Piperazines/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Proteins/antagonists & inhibitors ; Proteins/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/metabolism ; Purines/pharmacology ; Pyridines/pharmacology ; Pyrimidines/pharmacology ; Signal Transduction/drug effects ; Sulfonamides/pharmacology ; TOR Serine-Threonine Kinases ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/metabolism
Chemical Substances	ABT-737 ; Biphenyl Compounds ; CRTC2 protein, human ; Furans ; Indoles ; Multiprotein Complexes ; Nitrophenols ; PI103 ; Phosphoinositide-3 Kinase Inhibitors ; Piperazines ; Protein Kinase Inhibitors ; Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-myc ; Purines ; Pyridines ; Pyrimidines ; Sulfonamides ; Transcription Factors ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; PP242 (H5669VNZ7V)
Language	English
Publishing date	2012-01-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-11-0394
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Article ; Online: Inhibition of germinal centre apoptotic programmes by epstein-barr virus.

Spender, Lindsay C / Inman, Gareth J

Advances in hematology

2011 Volume 2011, Page(s) 829525

Abstract: To establish a persistent latent infection, Epstein-Barr virus (EBV) faces a challenge in that the virus-infected host cell must transit through the germinal centre reaction. This is a site of B cell differentiation where antibody responses are optimised, ...

Abstract	To establish a persistent latent infection, Epstein-Barr virus (EBV) faces a challenge in that the virus-infected host cell must transit through the germinal centre reaction. This is a site of B cell differentiation where antibody responses are optimised, and the selection criteria for B cells are stringent. The germinal centre environment is harsh, and the vast majority of B cells here die by apoptosis. Only cells receiving adequate survival signals will differentiate fully to be released into the periphery as long-term memory B cells (the site of persistence). In this review, we detail the apoptotic pathways potentially encountered by EBV-infected B cells during the process of infection, and we describe the functions of those EBV-regulated cellular and viral genes that help promote survival of the host B cell.
Language	English
Publishing date	2011-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2494501-8
ISSN	1687-9112 ; 1687-9112
ISSN (online)	1687-9112
ISSN	1687-9112
DOI	10.1155/2011/829525
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Article ; Online: Targeting the BCL-2 family in malignancies of germinal centre origin.

Spender, Lindsay C / Inman, Gareth J

Expert opinion on therapeutic targets

2009 Volume 13, Issue 12, Page(s) 1459–1472

Abstract: The germinal centre is a dynamic microenvironment where B-cell responses are honed. Antigen-specific cells undergo clonal expansion followed by antibody affinity maturation and class switching through somatic hypermutation and recombination of ... ...

Abstract	The germinal centre is a dynamic microenvironment where B-cell responses are honed. Antigen-specific cells undergo clonal expansion followed by antibody affinity maturation and class switching through somatic hypermutation and recombination of immunoglobulin genes respectively. The huge proliferative capacity of the B-cells and the potential for generating non-functional or autoreactive immunoglobulins, necessitate strict control measures. Pro-apoptotic signalling pathways via B-cell receptors, FAS and the TGF-beta receptor, ALK5, ensure that apoptosis of germinal centre B-cells is the norm and cells only survive to differentiate fully if they receive sufficient pro-survival signals to overcome their 'primed for death' status. Several of the B-cell signalling pathways converge on the intrinsic apoptotic machinery to control expression of the BCL-2 family of apoptosis regulators including BIM, the pro-survival factor BCL-X(L) and the BH3-only protein, BIK (recently identified as a mediator of a TGF-beta-induced default apoptosis pathway in human B-cells). It is a foreseeable hazard that cells undergoing genetic mutation and recombination events might unintentionally target some of these factors, resulting in defective programmed cell death. Here we discuss the function of BCL-2 family proteins in germinal centre reactions, their deregulation in malignancies of germinal centre origin, and the potential for targeting BCL-2-related proteins therapeutically in lymphomas.
MeSH term(s)	Animals ; B-Lymphocytes/drug effects ; Genes, bcl-2/drug effects ; Genes, bcl-2/genetics ; Germinal Center/physiology ; Humans ; Neoplasms/genetics
Language	English
Publishing date	2009-11-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1517/14728220903379565
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Article ; Online: Multifaceted transforming growth factor-beta (TGFβ) signalling in glioblastoma.

Birch, Joanna L / Coull, Barry J / Spender, Lindsay C / Watt, Courtney / Willison, Alice / Syed, Nelofer / Chalmers, Anthony J / Hossain-Ibrahim, M Kismet / Inman, Gareth J

Cellular signalling

2020 Volume 72, Page(s) 109638

Abstract: Glioblastoma (GBM) is an aggressive and devastating primary brain cancer which responds very poorly to treatment. The average survival time of patients is only 14-15 months from diagnosis so there is a clear and unmet need for the development of novel ... ...

Abstract	Glioblastoma (GBM) is an aggressive and devastating primary brain cancer which responds very poorly to treatment. The average survival time of patients is only 14-15 months from diagnosis so there is a clear and unmet need for the development of novel targeted therapies to improve patient outcomes. The multifunctional cytokine TGFβ plays fundamental roles in development, adult tissue homeostasis, tissue wound repair and immune responses. Dysfunction of TGFβ signalling has been implicated in both the development and progression of many tumour types including GBM, thereby potentially providing an actionable target for its treatment. This review will examine TGFβ signalling mechanisms and their role in the development and progression of GBM. The targeting of TGFβ signalling using a variety of approaches including the TGFβ binding protein Decorin will be highlighted as attractive therapeutic strategies.
MeSH term(s)	Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Decorin/metabolism ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Humans ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Tumor Microenvironment
Chemical Substances	Decorin ; Transforming Growth Factor beta
Language	English
Publishing date	2020-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2020.109638
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Article: TGF-beta induces growth arrest in Burkitt lymphoma cells via transcriptional repression of E2F-1.

Spender, Lindsay C / Inman, Gareth J

The Journal of biological chemistry

2008 Volume 284, Issue 3, Page(s) 1435–1442

Abstract: ... c-MYC, Id1, Id2, and Id3. Loss of c-MYC expression is a pivotal event in this process, resulting ... arrest in other cell types. Here, in human Burkitt lymphoma cells transformed by deregulated c-MYC ... expression, we demonstrate that efficient TGF-beta-induced cytostasis can occur despite both maintenance of c ...

Abstract	Transforming growth factor-beta (TGF-beta) is a potent regulator of tissue homeostasis and can act as both a tumor suppressor and a tumor promoter. The ability to induce cell cycle arrest is a major component of the tumor suppressor function of TGF-beta. Lung, mammary, and skin epithelial cells exhibit a common minimal cytostatic program in response to TGF-beta signaling involving the repression of the growth-promoting factors c-MYC, Id1, Id2, and Id3. Loss of c-MYC expression is a pivotal event in this process, resulting in derepression of the cyclin-dependent kinase inhibitors CDKN1A (p21) and CDKN2B (p15) and ultimately leading to growth arrest. It is not clear, however, which responses are necessary for TGF-beta-mediated growth arrest in other cell types. Here, in human Burkitt lymphoma cells transformed by deregulated c-MYC expression, we demonstrate that efficient TGF-beta-induced cytostasis can occur despite both maintenance of c-MYC levels and a lack of p21 and p15 induction. TGF-beta treatment also results in induction, rather than repression, of Id1 and Id2 expression. In this context, growth arrest correlates with transcriptional repression of E2F-1, and overexpression of E2F-1 in Burkitt lymphoma cells largely overcomes the TGF-beta-mediated G(1) arrest phenotype. These data indicate that deregulation of c-MYC in lymphoma cells does not overcome the tumor suppressor function of TGF-beta and that repression of E2F-1 transcription is sufficient for the efficient induction of cytostasis.
MeSH term(s)	Burkitt Lymphoma/genetics ; Burkitt Lymphoma/metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p15/genetics ; Cyclin-Dependent Kinase Inhibitor p15/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; E2F1 Transcription Factor/biosynthesis ; E2F1 Transcription Factor/genetics ; G1 Phase/drug effects ; G1 Phase/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Inhibitor of Differentiation Proteins/genetics ; Inhibitor of Differentiation Proteins/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Transcription, Genetic/drug effects ; Transcription, Genetic/genetics ; Transforming Growth Factor beta/pharmacology
Chemical Substances	CDKN1A protein, human ; CDKN2B protein, human ; Cyclin-Dependent Kinase Inhibitor p15 ; Cyclin-Dependent Kinase Inhibitor p21 ; E2F1 Transcription Factor ; E2F1 protein, human ; Inhibitor of Differentiation Proteins ; MYC protein, human ; Proto-Oncogene Proteins c-myc ; Transforming Growth Factor beta
Language	English
Publishing date	2008-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M808080200
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Article ; Online: Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: why clinical trials might have failed and how they could succeed.

Meemanage, Madusha / Spender, Lindsay C / Collinson, Diane / Iannetta, Joanna / Challapalli, Pranavi / Turbitt, Julie / Clark, Caroline / Baxter, Mark / Murray, Graeme / Walsh, Shaun / Miedzybrodzka, Zofia / Petty, Russell D

Cancer chemotherapy and pharmacology

2020 Volume 87, Issue 3, Page(s) 361–377

Abstract: Purpose: Oesophageal squamous cell carcinoma (ESCC) has a poor prognosis. Advanced tumours are treated with fluoropyrimidine/platinum chemotherapy followed by irinotecan or taxane monotherapy, but resistance is common and new treatments are needed. ... ...

Abstract	Purpose: Oesophageal squamous cell carcinoma (ESCC) has a poor prognosis. Advanced tumours are treated with fluoropyrimidine/platinum chemotherapy followed by irinotecan or taxane monotherapy, but resistance is common and new treatments are needed. Approximately 20% of ESCCs carry copy number gain (CNG) of the epidermal growth factor receptor (EGFR) gene. Previous trials show that while anti-EGFR monotherapy benefits biomarker-selected patients with EGFR CNG and/or high EGFR expression, combining anti-EGFR therapies with platinum fluoropyrimidine chemotherapies is not effective, and uncertainty remains regarding the optimal cytotoxic chemotherapy partner for anti-EGFR therapies in ESCC. Methods: The effects of EGFR CNG on fluoropyrimidine/platinum chemotherapy sensitivity in a cohort of gastroesophageal cancer patients (n = 302) was evaluated. Drug combination studies using the EGFR inhibitor gefitinib with cytotoxic chemotherapies, docetaxel, cisplatin, oxaliplatin and irinotecan, on cell proliferation and cell death of EGFR CNG ESCC cell lines were assessed. Results: EGFR CNG in gastroesophageal cancer patients was associated with improved overall survival following fluoropyrimidine/platinum chemotherapy. However, co-administration of gefitinib and oxaliplatin or cisplatin was frequently antagonistic in cell-based assays in EGFR CNG ESCC, whereas the combination of gefitinib with docetaxel or irinotecan was more efficacious. Co-administration of gefitinib/docetaxel and sequential administration of docetaxel before gefitinib showed synergy, but docetaxel given after gefitinib was antagonistic. Conclusion: Gefitinib/platinum co-administration demonstrated antagonism suggesting a possible explanation for the lack of benefit from addition of anti-EGFR therapies to fluoropyrimidine/platinum chemotherapy in trials. Gefitinib/docetaxel co-administration demonstrated synergy suggesting taxanes could be the most effective cytotoxic partner for anti-EGFR therapies in EGFR CNG-positive ESCC, but careful consideration of drug scheduling is required.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cohort Studies ; Drug Synergism ; ErbB Receptors/antagonists & inhibitors ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/pathology ; Esophageal Squamous Cell Carcinoma/drug therapy ; Esophageal Squamous Cell Carcinoma/pathology ; Female ; Gefitinib/administration & dosage ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate
Chemical Substances	EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Gefitinib (S65743JHBS)
Language	English
Publishing date	2020-11-09
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-020-04187-w
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