www.nature.

com/reviews

CANCER CLINICAL ONCOLOGY

Produced with support from:

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 2013 Macmillan Publishers Limited. All rights reserved

CANCER

he Nature Reviews Cancer calendar for 2014 has a clinical twist. As well as plundering our own image bank for more clinically oriented figures, we have chosen six images and figures from our sister journal, Nature Reviews Clinical Oncology. All of

these images convey some of the important aspects of clinical cancer research, thus producing a bench to bedside and back again overview. At the end of the calendar we have included some additional Reviews and Perspectives that discuss important topics that are related to each figure, such as biomarkers, targeted therapies, cancer imaging, detection and diagnosis. We have also included images that focus on particular types of cancer, such as ovarian, lung and prostate. As always, we are indebted to our authors for producing such good ideas for figures and the excellent articles that go with them. We hope that you find this calendar of use and we look forward to meeting some of you at the 2014 cancer-related conferences that are listed in the back of the calendar. Our calendar is freely available thanks to support from OriGene.
Nature Reviews Cancer: http://www.nature.com/nrc/index.html Nature Reviews Clinical Oncology: http://www.nature.com/nrclinonc/index.html Follow @NatureRevCancer and @NatRevClinOncol on Twitter: http://twitter.com/NatureRevCancer http://twitter.com/NatRevClinOncol Calendar compiled and edited by Nicola McCarthy and Lisa Hutchinson Copy-edited by Simon Neil Designed and illustrated by Lara Crow

LIST OF ABBREVIATIONS USED IN THE CALENDAR: CAIX, carbonic anhydrase 9; COX-2, cyclooxygenase2; CRC, colorectal cancer; ctDNA, circulating tumour DNA; CXCR, CXC-chemokine receptor; ECM, extracellular matrix; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; FGF, fibroblast growth factor; FGFR, FGF receptor; FOXO3A, forkhead box O3A; FVIIa, factor VIIa; GPVI, glycoprotein 6; GPIb, glycoprotein inhibitor b; HDAC, histone deacetylase; HGF, hepatocyte growth factor; HGPIN, high-grade prostatic intraepithelial neoplasia; HIF-1, hypoxia-inducible factor 1; ICAM, intercellular adhesion molecule; IL, interleukin; mTOR, mammalian target of rapamycin; NF-B, nuclear factor-B; PAR, prostate apoptosis response; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; PGE2, prostaglandin E2; PPAR, peroxisomal proliferator-activated receptor-; PSGL1, P selectin ligand 1; SDF1, stromal cell-derived factor 1; sLe, sialyl Lewis antigen; TCF, transcription factor 1; TGF, transforming growth factor-; TSC, tuberous sclerosis; VCAM, vascular cellular adhesion molecule; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; VHL, Von HippelLindau; VWF, Von Willebrand factor. Streamline your gene-related research with OriGenes broad gene centric tools for molecular and cellular research. Our product offering includes: 30,000 validated antibodies 200,000 expression cDNA clones, with or without tags 200,000 RNAi reagents (shRNA , siRNA and miRNA) 10,000 purified human proteins from human cells 140,000 human tissues for cancer research Constructing any plasmid vectors via gene synthesis Type the name of your favorite gene into OriGenes search box and be amazed. Join thousands of scientists who experienced the quality and convenience of OriGenes tools. Put your project into power drive! (www.origene.com)

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Red blood cell Healthy cell Circulating tumour cell Healthy tissue

Apoptosis or necrosis

Phagocyte

Tumour cell Mutation Apoptosis

Chromosome

Inamed tissue Blood plasma or serum sample containing ctDNA

Endothelial cell

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Biomarkers

JANUARY
SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

5 12 19 26 6 13 20 27 7 14 21 28

1 8 15 22 29

2 9 16 23 30

3 10 17 24 31

4 11 18 25

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 2013 Macmillan Publishers Limited. All rights reserved

Cancer imaging optical coherence tomography-based angiography of a murine mammary carcinoma grown in a dorsal skin flap

CANCER
SUNDAY MONDAY TUESDAY

FEBRUARY
WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 2 9 16 23 3 10 17 24 4 11 18 25 5 12 19 26 6 13 20 27 7 14 21 28 8 15 22

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Dysplastic polyp PGE2

Stem cell re-programming Aberrant DNA methylation PGE2 Chemokines Cytokines IL-6 IL-8 Inammatory stroma Aspirin EGFR signalling Immunosuppressive stroma Epigenetic repression of mismatch repair genes

Cancer

Aspirin Myeloid-derived suppressor cell High COX-2 expression on invasive front

Cancer cell Macrophage

Reduce E cadherin

Immature dendritic cell

Epithelialmesenchymal transition Cytokines

Aspirin

Angiogenesis

Apoptosis in CRC stem cells

Warburg eect

NF-B

Aspirin

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Colon cancer

MARCH
SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 2 9 16 23 30 3 10 17 24 31
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4 11 18 25

5 12 19 26

6 13 20 27

7 14 21 28

8 15 22 29

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Seminal vesicles

ETS fusionnegative

ETS fusionpositive

Benign

Lung Liver

Apex

HGPIN

Localized prostate cancer Metastasis

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Prostate cancer

CANCER
SUNDAY MONDAY TUESDAY WEDNESDAY

APRIL
THURSDAY

2014
SATURDAY

FRIDAY

1 6 13 20 27 7 14 21 28 8 15 22 29

2 9 16 23 30

3 10 17 24

4 11 18 25

5 12 19 26

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Cell cycle an image of dividing HeLa cells, which was provided by Mark Petronczki, Cancer Research UK London Research Institute, London, UK

MAY
SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 4 11 18 25 5 12 19 26 6 13 20 27 7 14 21 28 8 15 22 29

2 9 16 23 30

3 10 17 24 31

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Immune cell Blood vessels Myoepithelial cells Lymphatics

ECM

Genetically abnormal malignant progenitor cells arise in zone of hypoxic stress

Stromal cells Central necrosis Calcium spicule

Microinvasion of malignant progenitor cells

Fat cells

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Diagnosis

CANCER
SUNDAY MONDAY TUESDAY WEDNESDAY

JUNE
THURSDAY

2014
SATURDAY

FRIDAY

1 8 15 22 29

2 9 16 23 30

3 10 17 24

4 11 18 25

5 12 19 26

6 13 20 27

7 14 21 28

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 2013 Macmillan Publishers Limited. All rights reserved

Brain cancer an image of human differentiated glioma stem cells, which was provided by Kathreena M. Kurian of Frenchay Hospital, University of Bristol, UK

JULY
SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 6 13 20 27 7 14 21 28 8 15 22 29

2 9 16 23 30

3 10 17 24 31

4 11 18 25

5 12 19 26

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Tumour cell

Cohesion Platelet microparticles Growth factors Chemokines Proteases

Activated platelet

Coagulation

Leukocyte Tissue factor and FVIIa activate thrombin

Adhesion Thrombin Integrin IIb3 Integrin v3 Integrin M2 PAR4 PAR1 and PAR2 sLex and sLea VWF CD44 GPVI Fibrinogen GPIb PSGL1 L-selectin E-selectin P-selectin Mucins Immune evasion

WiebelPalade bodies ICAM and VCAM

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Natural killer cell

Metastasis

CANCER
SUNDAY MONDAY TUESDAY WEDNESDAY

AUGUST
THURSDAY

2014
SATURDAY

FRIDAY

1 3 10 17 24 31
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2 9 16 23 30

4 11 18 25

5 12 19 26

6 13 20 27

7 14 21 28

8 15 22 29

Fibroblasts and stroma

Dovitinib VEGFRs PDGFR

Growth factor receptors HGF FGF SDF1

VEGF

EGFR

EGF

MET

FGFRs

Bevacizumab

Sunitinib Pazopanib Sorafenib Axitinib Tivozanib

Dovitinib RAF RAS PI3K CXCR4

MEK BEZ235 and other PI3KAKT inhibitors

AKT

PTEN CAIX HIF-1

Invasion metastasis

MAPK

Angiogenesis

Other proangiogenic factors: IL-8 PDGF TGF Angiopoietin FGF

VHL Cell proliferation and survival S6-kinase mTOR Temsirolimus Everolimus

TSC2 TSC1

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Kidney cancer

SEPTEMBER
SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 7 14 21 28 8 15 22 29

2 9 16 23 30

3 10 17 24

4 11 18 25

5 12 19 26

6 13 20 27

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Stomach

Fallopian tube

Colon Ovary

Appendix

Retrograde menstruation

Uterus

Mucinous invasive

Endometrioid

Clear cell

High-grade serous

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Ovarian cancer

CANCER
SUNDAY MONDAY TUESDAY WEDNESDAY

OCTOBER
THURSDAY

2014
SATURDAY

FRIDAY

1 5 12 19 26 6 13 20 27 7 14 21 28 8 15 22 29

2 9 16 23 30

3 10 17 24 31

4 11 18 25

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 2013 Macmillan Publishers Limited. All rights reserved

Drug response an image of human colon carcinoma provided by Irene Chicote and Hctor G. Palmer, Vall dHebron Institute of Oncology, Barcelona, Spain

NOVEMBER
SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 2 9 16 23 30
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3 10 17 24

4 11 18 25

5 12 19 26

6 13 20 27

7 14 21 28

8 15 22 29

Central compartment

Large bronchus

Ciliated cell Mucous cell

Primary bronchus Neuro-endocrine cell Secondary bronchus Tertiary bronchus Bronchiole Terminal bronchiole Alveoli Alveolus Respiratory bronchiole Clara cell Respiratory bronchiole Basal cell Basement membrane

Peripheral compartment Respiratory bronchiole

Ciliated cell Basement membrane Interstitium Type I pneumocyte

Alveolar duct Alveolus

Type II pneumocyte

Alveolus

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Lung cancer

CANCER
SUNDAY MONDAY TUESDAY

DECEMBER
WEDNESDAY THURSDAY

2014
SATURDAY

FRIDAY

1 7 14 21 28 8 15 22 29

2 9 16 23 30

3 10 17 24 31

4 11 18 25

5 12 19 26

6 13 20 27

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READING LIST JANUARY

BIOMARKERS
Adapted from Crowley, E. et al. Liquid biopsy: monitoring cancer-genetics in the blood. Nature Rev. Clin. Oncol. 10, 472484 (2013) FURTHER READING Schwarzenbach, H., Hoon, D. S. B. & Pantel, K. Cell-free nucleic acids as biomarkers in cancer patients. Nature Rev. Cancer 11, 426437 (2011) De Mattos-Arruda, L., et al. Circulating tumour cells and cell-free DNA as tools for managing breast cancer. Nature Rev. Clin. Oncol. 10, 377389 (2013) Hanash, S. M., Baik, C. S. & Kallioniemi, O. Emerging molecular biomarkers blood-based strategies to detect and monitor cancer. Nature Rev. Clin. Oncol. 8,142150 (2011)

FEBRUARY
CANCER IMAGING
Adapted from Vakoc, B. J., Fukumura, D., Jain, R. K. & Bouma, B. E. Cancer imaging by optical coherence tomography: preclinical progress and clinical potential. Nature Rev. Cancer 12, 363368 (2012). Image is reproduced, with permission, from Vakoc, B. J. et al. Nature Med. 15, 12191223 (2009) (2009) Macmillan Publishers Ltd. All rights reserved. FURTHER READING Nguyen, Q. T. & Tsien, R. Y. Fluorescence-guided surgery with live molecular navigation a new cutting edge. Nature Rev. Cancer 13, 653662 (2013) Morgan, B. Opportunities and pitfalls of cancer imaging in clinical trials. Nature Rev. Clin. Oncol. 8, 517527 (2011) Focus on Imaging www.nature.com/nrclinonc/focus/ imaging

MARCH
COLON CANCER
Adapted from Chia, W. K., Ali, R. & Toh, H. C. Aspirin as adjuvant therapy for colorectal cancer reinterpreting paradigms. Nature Rev. Clin. Oncol. 9, 561570 (2012) FURTHER READING Langley, R. E. & Rothwell, P. M. Biological markers: Potential biomarker for aspirin use in colorectal cancer therapy. Nature Rev. Clin. Oncol. 10, 810 (2013) Thun, M. J., Jacobs, E. J. & Patrono, C. The role of aspirin in cancer prevention. Nature Rev. Clin. Oncol. 9, 259267 (2012) Wang, D. & DuBois, R. N. Eicosanoids and cancer. Nature Rev. Cancer 10, 181193 (2010)

APRIL
PROSTATE CANCER
Adapted from Kumar-Sinha, C., Tomlins, S. A. & Chinnaiyan, A.M. Recurrent gene fusions in prostate cancer. Nature Rev. Cancer 8, 497511 (2008) FURTHER READING Sutcliffe, S. & Colditz, G. A. Prostate cancer: is it time to expand the research focus to early-life exposures? Nature Rev. Cancer 13, 208218 (2013) Risbridger, G. P., Davis, I. D., Birrell, S. N. & Tilley, W. D. Breast and prostate cancer: more similar than different. Nature Rev. Cancer 10, 205212 (2010) Scher, H. I., Morris, M. J., Larson, S. & Heller, G. Validation and clinical utility of prostate cancer biomarkers. Nature Rev. Clin. Oncol. 10, 225234 (2013)

MAY
CELL CYCLE
Adapted from the 2011 cover of Nature Rev. Clin. Oncol. The image shows human cancer cell lines (HeLa) with -tubulin pseudo-coloured red, DNA in blue and the midbody pseudocoloured green. FURTHER READING Alcolea, M. P. & Jones, P. H. Tracking cells in their native habitat: lineage tracing in epithelial neoplasia. Nature Rev. Cancer 13, 161171 (2013) Sadasivam, S. & DeCaprio, J. A. The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nature Rev. Cancer 13, 585595 (2013) Komlodi-Pasztor, E., Sackett, D., Wilkerson, J. & Fojo, T. Mitosis is not a key target of microtubule agents in patient tumors. Nature Rev. Clin. Oncol. 8, 244-250 (2011)

JUNE
DIAGNOSIS
Adapted from Espina, V. & Liotta, L. A. What is the malignant nature of human ductal carcinoma in situ? Nature Rev. Cancer 11, 6875 (2011) FURTHER READING Hamilton, W. Diagnosis: Cancer diagnosis in UK primary care. Nature Rev. Clin. Oncol. 9, 251252 (2012) Lao-Sirieix, P. & Fitzgerald, R. C. Screening for oesophageal cancer. Nature Rev. Clin. Oncol. 9, 278287 (2012) Kulasingam, V., Pavlou, M. P. & Diamandis, E. P. Integrating high-throughput technologies in the quest for effective biomarkers for ovarian cancer. Nature Rev. Cancer 10, 371378 (2010)

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JULY
BRAIN CANCER
Adapted from the 2012 cover of Nature Rev. Clin. Oncol. An immunofluorescence image of primary culture differentiated human glioma stem cells derived from adult glioblastoma. Cells have pleomorphic nuclei and lack of contact inhibition. FURTHER READING Tanaka, S., Louis, D. N., Curry, W. T., Batchelor, T. T. & Dietrich, J. Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? Nature Rev. Clin. Oncol. 10, 1426 (2013) Steeg, P. S., Camphausen, K. A. & Smith, Q. R. Brain metastases as preventive and therapeutic targets. Nature Rev. Cancer 11, 352363 (2011) Huse, J. T. & Holland, E. C. Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma. Nature Rev. Cancer 10, 319331 (2010)

AUGUST
METASTASIS
Adapted from Gay, L. J. & Felding-Habermann, B. Contribution of platelets to tumour metastasis. Nature Rev. Cancer 11, 123134 (2011) FURTHER READING De Craene, B. & Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nature Rev. Cancer 13, 97110 (2013) Brabletz, T. To differentiate or not routes towards metastasis. Nature Rev. Cancer 12, 425436 (2012) Mina, L. A. & Sledge, G. W Jr. Rethinking the metastatic cascade as a therapeutic target. Nature Rev. Clin. Oncol. 8, 325332 (2011) Focus on Migration and metastasis www.nature.com/nrc/ focus/migration

SEPTEMBER
KIDNEY CANCER
Adapted from Bellmunt, J., Teh, B. T., Tortora, G. & Rosenberg, J. E. Molecular targets on the horizon for kidney and urothelial cancer. Nature Rev. Clin. Oncol. 10, 557570 (2013) FURTHER READING Escudier, B., Szczylik, C., Porta, C. & Gore, M. Treatment selection in metastatic renal cell carcinoma: expert consensus. Nature Rev. Clin. Oncol. 9, 327337 (2012) Huff, V. Wilms tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nature Rev. Cancer 11, 111121 (2011) Biswas, S. & Eisen, T. Immunotherapeutic strategies in kidney cancer when TKIs are not enough. Nature Rev. Clin. Oncol. 6, 478487 (2009)

OCTOBER
OVARIAN CANCER
Adapted from Vaughan, S. et al., Rethinking ovarian cancer: recommendations for improving outcomes. Nature Rev. Cancer 11, 719725 (2011) FURTHER READING Johnson, P. A. & Giles, J. R. The hen as a model of ovarian cancer. Nature Rev. Cancer 13, 432436 (2013) Kipps, E., Tan, D. S. P. & Kaye, S. B. Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research. Nature Rev. Cancer 13, 273282 (2013) Coleman, R. L., Monk, B. J., Sood, A. K. & Herzog, T. J. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nature Rev. Clin. Oncol. 10, 211224 (2013)

NOVEMBER
DRUG RESPONSE
Adapted from the 2013 cover of Nature Rev. Clin. Oncol. Immunofluorescence staining for -catenin and FOXO3A proteins as potential markers for the prediction of drug response in a histological section of a human colon carcinoma. FURTHER READING Kuczynski, E. A., Sargent, D. J., Grothey, A. & Kerbel, R. S. Drug rechallenge and treatment beyond progression implications for drug resistance. Nature Rev. Clin. Oncol. http://dx.doi.org/10.1038/ nrclinonc.2013.158 (2013) La Thangue, N. B. & Kerr, D. J. Predictive biomarkers: a paradigm shift towards personalized cancer medicine. Nature Rev. Clin. Oncol. 8, 587596 (2011)

DECEMBER
LUNG CANCER
Adapted from Sun, S., Schiller, J. H. & Gazdar, A. F. Lung cancer in never smokers a different disease. Nature Rev. Cancer 7, 778790 (2007) FURTHER READING Houghton, A. M. Mechanistic links between COPD and lung cancer. Nature Rev. Cancer 13, 233245 (2013) Pao, W. & Chmielecki, J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nature Rev. Cancer 10, 760774 (2010) Mok, T. S. Personalized medicine in lung cancer: what we need to know. Nature Rev. Clin. Oncol. 8, 661668 (2011)

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CALENDAR OF EVENTS
Sunday 5 12 26 Monday 6 13 27 Tuesday 7 14 28 Wednesday 1 JANUARY 8 15 22 Thursday 2 9 16 23 Friday 3 10 17 24 4 11

2014
Saturday 18 AACR-Prostate 25

19 cancer foundation conference, California, USA

29 AACR: Cancer susceptibility and susceptibility syndromes, California, USA 1

FEBRUARY

2 Keystone: Developmental pathways in cancer; and Stem cells and cancer, Banff, Canada 6 9 16 23 10 17 24 11 18 25 12 19 26 20 27

7 21 28

8 22

13 26th Lorne cancer conference, Victoria, Australia

1 MARCH 2 3 4 9 Keystone: Immune evolution in cancer, Whistler, Canada 16 Keystone: Tumor metabolism, Whistler, Canada 23 30 6 APRIL 13 20 27 31 1
Meeting, California, USA

5 12 19

6 13 20 27 3 10 17 24

7 14 21 28 4 11 18 25

8 15 22 29 5 AACR Annual 12 19 26

24 30th Genes and cancer meeting, Cambridge, UK 2 9 16 23 30

8 15 22 29

14 21 28

1 4 MAY 11 18 5 12 6 13 20 27 3 10 17 24 7 14 21 28

2 3 8 IMPAKT 2014 Breast cancer conference, Brussels, Belgium 15 22 29 16 17 23 EMBO conference: Cellular signalling 30 50th ASCO Annual Meeting, Illinois, USA 7 14 21 28

19 25 and cancer therapy, Cavtat, Croatia 1 8 2 9 16 23 30

4 GRC: Cell polarity signaling, Massachusetts, USA 11 18 25 12 19 26 13 20 27

JUNE

15 22 29

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Sunday

Monday

Tuesday 1

Wednesday 2 9 16 23 30

Thursday 3 10 17 24 31

Friday 4 11 18 25

Saturday 5 23rd Biennial 12 19 26

6 Congress of the EACR, Munich, Germany 8 JULY 13 20 27 14 21 28 15 22 29

1 AUGUST 3 GRC: Rare cells in circulation, Massachusetts, USA 10 17 24 31 1 SEPTEMBER 7 14 21 28 8 15 22 29 2 9 16 23 30 1 OCTOBER 5 12 19 6 13 20 7 14 21 8 15 22 2 9 16 23 3 10 17 24 31 3 10 17 24 4 11 18 25 5 12 19 11 18 25 12 19 26 6 13 20 27 7 14 21 28 8 15 22 29

2 9 16 23 30 6 13 20

26 ESMO 2014 Congress, Madrid, Spain

4 11 18 25

26 AACR: Translational Cancer Research for Basic Scientists Workshop, Massachusetts, USA

1 NOVEMBER 2 9 16 23 30 1 DECEMBER 7 14 21 28 8 15 22 29 2 16 23 30 3 World Cancer Congress, Melbourne, Australia 12 19 26 17 24 31 18 25 6 13 20 27 9 San Antonio Breast Cancer Symposium, Texas, USA 3 10 17 24 4 11 25 5 12 26 6 13 27 7 14 21 28 8 15 22 29

18 EORTCAACRNCI International symposium, Barcelona, Spain

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4 Crinan Street, London, N1 9XW www.nature.com/nrc www.nature.com/nrclinonc

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