sectionOne-bg
sectionOne-bg

This is a healthcare professional site

The information contained in the site is intended for Canadian healthcare professionals only. Please select your province or territory and enter your medical licence number to access the website.

Please select a province or territory.

Incorrect PIN - Contact Us

Please enter a first name

Please enter a last name

Please enter a valid email address


Please accept the terms and conditions.


sectionOne-bg
sectionOne-bg
sectionOne-bg_image
sectionOne-bg_image
DISCOVER HOW

investigational biomarkers may play a role in navigating the landscape of metastatic gastric/gastro-esophageal junction cancer pathophysiology.

SCROLL TO EXPLORE SCROLL TO EXPLORE
cloud image
cloud image

 

 

 

Despite a landscape clouded in complexity, investigational biomarkers are expanding our view of the pathophysiology of gastric cancer, and biomarker testing could provide a more comprehensive understanding of this disease.

 

Exploring biomarker advancements starts here.
SCROLL TO EXPLORE
landscape_image
landscape_image
WELCOME TO

The Gastric Cancer Disease Landscape

SELECT A BIOMARKER BELOW

 

 

CLDN18.2=claudin 18.2; FGFR2b=fibroblast growth factor receptor 2b; HER2=human epidermal growth factor receptor 2; MSI=microsatellite instability; PD-L1=programmed death-ligand 1.

SCROLL TO EXPLORE

INTRO

Overview of gastric/gastroesophageal junction (G/GEJ) cancers

 

In Canada, estimates indicate that age-standardized 5-year net survival of patients diagnosed with stomach cancer is 25% (2008–2010).*,1

* Age-standardized 5-year net survival estimates for primary sites of cancer, both sexes, three years combined.

6% 5-year survival rate of mGC in the US.

IN CANADA

Among patients who survive at least one year after diagnosis, approximately 55% survive for 5 years post-diagnosis (2015–2017).†,2

55% survive for 5 years post-diagnosis

In 2022, it was estimated that 4100 new cases of stomach cancers would be diagnosed in Canada (excluding Quebec).3   

4100 NEW CASES

†  Ages 15–99 years in Canada (excluding Quebec).

AROUND THE WORLD

An estimated 769,000 people died worldwide in 2020 due to G/GEJ cancers, making it the 4th most deadly cancer.4

Over 1 million new cases of G/GEJ cancers were diagnosed worldwide in 2020, making it the 5th most diagnosed cancer.4

In 2018, the global overall 5-year survival rate was approximately ≤10% in mGC.5

As biomarkers are investigated, they reveal new insights into mG/GEJ cancer pathophysiology6

 

INVESTIGATIONAL BIOMARKERS

  • CLDN18.2 (claudin 18.2), as a component of tight junctions, has a role in cell-to-cell epithelial adhesion and regulating selective barrier properties7-9
  • FGFR2b (fibroblast growth factor receptor 2b) is a splice variant of FGFR2, a transmembrane signaling pathway that intermediates diverse cellular behaviors and cellular processes, such as mitogenesis, differentiation, cell proliferation, angiogenesis, and invasion10,11

KNOWN BIOMARKERS

  • HER2 (human epidermal growth factor receptor 2) is a key driver of tumourigenesis, where it is implicated in tumour cell proliferation, apoptosis, adhesion, migration, and differentiation6,12
  • MSI (microsatellite instability) is characterized by somatic alterations in microsatellite sequences that are associated with genomic instability8,10,13
  • PD-L1 (programmed death-ligand 1) can bind to the immune checkpoint receptor PD-1 (programmed cell death protein 1) which allows tumours to escape immune surveillance6,14

Investigational and known biomarkers can be detected by standard IHC staining methods.

 

INVESTIGATIONAL BIOMARKERS
 

CLDN18.2:
IHC8

FGFR2b:
IHC, ctDNA§,11,15

§ FGFR2b overexpression can be determined by IHC; FGFR2 gene amplification can be determined by ctDNA.11,15

 

KNOWN BIOMARKERS
 

PD-L1:
IHC||,6

HER2:
IHC, ISH, NGS¶,6,16

MSI/MMR:
PCR/NGS, IHC6

ctDNA=circulating tumour DNA; IHC=immunohistochemistry; ISH=in situ hybridization; MMR=mismatch repair; NGS=next generation sequencing; PCR=polymerase chain reaction.
|| Varying diagnostic assays.17
Other ISH methods (CISH=chromogenic ISH; DDISH=dual-color dual-hapten ISH; FISH=fluorescent ISH; SISH=silver ISH).16




Investigational biomarkers are prevalent among mG/GEJ biomarkers.
 

Biomarker prevalence estimates from select international studies are reported below. Prevalence data can vary among studies due to tumour heterogeneity, differences in patient population, clinical trial methodology, and diagnostic assays used.8,12,18-21

INVESTIGATIONAL BIOMARKERS

CLDN18.28
(high expression)

29% primary cases
34% nodal metastases

FGFR2b18
(overexpressed)#

3–61%

# Overexpression determined by IHC.18

 

KNOWN BIOMARKERS

PD-L119,20
(Variable due to multiple factors)**

CPS ≥1: 67–73%
CPS ≥5: 29–31%
CPS ≥10: 16–18%

HER213
(Positive)

22%

MSI21
(MSI-high)

4%

CPS=combined positive score.

** Prevalence of PD-L1 at various CPS thresholds was explored.19

CLDN18.2
(Claudin18.2)

CLDN18.2 gastric cancer biomarker

CLDN18.2

CLDN18.2 is an investigational biomarker that may help you learn more about your patients with mG/GEJ cancer8



Claudins are a family of transmembrane proteins:9,22


Claudins are a major component of epithelial and endothelial tight junctions, which are involved in controlling the flow of molecules between cells.7-9


Claudins are present throughout the body, but two specific isoforms of CLDN18 are localized to certain tissue types:9,22

  •  CLDN18.2 is the dominant isoform in normal, healthy gastric epithelial cells
  •  CLDN18.1 is the dominant isoform in normal, healthy lung tissue

 

Preclinical studies have shown that CLDN18.2 may be exposed in gastric tumours.9

 

CONFINED IN
HEALTHY TISSUE

 

CLDN18.2 in healthy gastric epithelial cells.
CLDN18.2 in healthy gastric epithelial cells.

 


In gastric epithelial cells, CLDN18.2 is typically buried in the tight junction supramolecular complex.8,9

It functions to regulate selective barrier properties and contribute to cell-to-cell epithelial adhesion.8,9

RETAINED DURING TRANSFORMATION

 

 

CLDN18.2 in healthy gastric epithelial cells.
CLDN18.2 in healthy gastric epithelial cells.



 

The presence of CLDN18.2 is retained throughout malignant transformation, both in the primary tumour site and metastatic disease.23

 


CLDN18.2 may be expressed when tumours develop in pancreatic, lung, and ovarian tissues as well.9,23

Detecting the presence of CLDN18.2 identifies a potentially undefined patient population



An international study indicated that approximately 62% of primary gastric cancers and 55% of nodal metastases expressed CLDN18.2 (at any level), and approximately 29% and 34% of patients are CLDN18.2 positive (high expression), respectively.*,8

 

* Study population was limited to 523 patients with gastric (n=408) and gastro-esophageal (n=115) cancers, of which 195 patients had high expression of CLDN18.2.8

  • Among investigational and known mG/GEJ biomarkers, CLDN18.2+ is highly prevalent
  • Detecting CLDN18.2 can be accomplished by standard IHC staining methods, as with many other biomarkers8

 

When evaluating the relationship between CLDN18.2 and other biomarkers, data from an international study suggests there is limited overlap.

  • In a real-world mono-institutional study, CLDN18.2+ (high expression) samples overlapped with 30% of MSI samples*,8

    • CLDN18.2 expression overlapped with PD-L1 in 39% of gastric cancer samples and 30% of gastro-esophageal cancer samples
    • CLDN18.2+ samples were also positive for the following biomarkers:

      •  

 

* Study population was limited to 523 patients with gastric (n=408) and gastro-esophageal (n=115) cancers, of which 195 patients had high expression of CLDN18.2. FGFR2b was not evaluated in this study.8

MMRd=mismatch repair deficient

 

CLDN18.2 is expressed in both diffuse-type tumours and intestinal-type tumours.8

FGFR2b
(fibroblast growth factor receptor 2b)

FGFR2b gastric cancer biomarker

FGFR2b

FGFR2b is an investigational biomarker that is found in a subset of patients with mG/GEJ cancer11

 

FGFR signaling mediates mitogenesis, differentiation, cell proliferation, angiogenesis and invasion.10

  • FGFR2 (fibroblast growth factor receptor 2) is a receptor tyrosine kinase that has a role in normal cell development24
  • The splice variant FGFR2b is expressed in various types of epithelial cells where tumours may begin to grow (including pancreatic, breast, endometrial, and lung cancers).24,25
  • FGFR2b may be associated with higher T stage (size of the tumour and any spread into nearby tissue) and higher N stage (extent of nodal metastases)11,26

 

FGFR2b overexpression has been reported in up to 15%, and positivity has been observed in 3–61%, of mG/GEJ cancers.*,18 These data were reported in an international study.


* FGFR2b positivity: overexpression (IHC) and/or gene amplification.

 

Detecting FGFR2b overexpression can be done with the following tests.11,15

  • FGFR2b overexpression by IHC
  • FGFR2 gene amplification by ctDNA

 

HER2
(human epidermal growth factor receptor 2)

HER2 gastric cancer biomarker

HER2

HER2 was the first biomarker used to guide clinical decisions in mG/GEJ cancer10



HER2 (human epidermal growth factor receptor 2) is a receptor-tyrosine kinase that is overexpressed and/or amplified in mG/GEJ cancer.6,10

  • HER2 is a proto-oncogene that is involved in signaling pathways, which leads to cell growth and differentiation.16
  • Studies have shown HER2 is present in several cancers, including colorectal, ovarian, prostate, lung, gastric, and gastroesophageal tumours16
  • When HER2 is overexpressed and/or amplified, it can lead to uncontrolled cell growth and tumourigenesis:12

    • However, the mechanisms that lead to gene amplification remain largely unknown27

HER2 positivity has been reported in an international study in 
22% of advanced G/GEJ cancers.12

 



HER2 positivity: overexpression (IHC3+) and/or gene amplification (FISH positive)



Detection of HER2 may be done with IHC, ISH methods and NGS, and is generally more associated with the intestinal type.*,6,12,16

  • Guidelines recommend starting with IHC and following with ISH methods only when expression is 2+ (equivocal)6

    • ISH methods include fluorescent in situ hybridization (FISH), silver in situ hybridization (SISH), chromogenic in situ hybridization (CISH), dual-color dual-hapten in situ hybridization (DDISH)6,16
  • Positive (3+) or negative (0 or 1+) IHC results do not require further testing via ISH6

* IHC/ISH should be considered first, followed by additional NGS testing as appropriate.6

MSI
(microsatellite instability)

MSI gastric cancer biomarker

MSI

MSI is a known biomarker that can be found in a broad range of solid tumour types, including mG/GEJ cancer13



MSI is associated with genomic instability and increased susceptibility to tumour development.10

Microsatellites are repeated sequences of nucleotides in DNA.13

  • Microsatellite instability (MSI) represents phenotypic evidence that the DNA mismatch repair (MMR) system is not functioning normally:13

    • This loss prevents normal repair and correction of DNA, allowing mismatches to occur13
    • The MMR proteins are the most frequently mutated genes in cancer13
  • Tumours with ≥30% expression of unstable microsatellites are referred to as MSI-high (MSI-H), while tumours with 10–29% expression are considered MSI-low.10 These data were reported in an international study.
  • MSI is found most often in colorectal cancer, gastric cancer, and endometrial cancer, but it may also be found in many other types of cancer13

 


MSI-H has been reported in an international study in 4% of mG/GEJ cancers.21




Detection of MSI is typically assessed with various methods.6

  • MSI gene expression can be detected via PCR-based molecular testing and NGS
  • MMR protein expression can be analyzed via IHC

PD-L1
(programmed death-ligand 1)

PD-L1 gastric cancer biomarker

PD-L1

PD-L1 is another known biomarker in mG/GEJ cancer that is used in clinical decision-making6



PD-L1 (programmed death-ligand 1) is a transmembrane protein that may be expressed on various tumour cells and/or immune cells.28

  • When bound to PD-1, PD-L1 acts as a T-cell inhibitory molecule, leading to immune cell evasion and subsequent tumour cell survival28
  • PD-L1 expression has been detected in various tumours, including lung, colon, ovarian and gastric cancers29
  • However, the cellular process of expression may not always be the same throughout the body17

    • Various studies have shown discordant levels of PD-L1 in the primary tumour vs. metastatic lesions17

 

Prevalence of PD-L1 has been reported for several positivity thresholds throughout various international studies: 67–73% CPS ≥1, 29–31% CPS ≥5, and 16–18% CPS ≥10.*,†,19,20

* Study population was limited to 592 patients with locally advanced or metastatic mG/GEJ cancer who experienced disease progression after first-line therapy with a platinum and fluoropyrimidine.20

† Study analyzed 56 specimens from therapy-naïve biopsies or post-neoadjuvant treatment from German patients with primarily non-metastatic gastric adenocarcinoma.19

 

 

  • The variations in prevalence may be due to several factors, such as tumour heterogeneity and clinical trial methodology (including differences in patient population, staining techniques, scoring algorithms, and diagnostic assays)17,30
  • Expression levels may also vary during disease progression, as PD-L1 is impacted by changes in immune response17

PD-L1 expression is detected using IHC.6

SUMMARY

Initial diagnostic panels that include biomarker testing may help provide a more comprehensive profile of gastric cancer in patients with this disease

 

NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer support biomarker testing.6

  • Biomarker testing has an important role in the diagnosis, classification, and molecular characterization of GC


The NCCN Guidelines recommend:

  • Testing for all known biomarkers (e.g., HER2, MSI, PD-L1) at diagnosis if metastatic cancer is documented or suspected
  • The use of IHC/FISH/targeted PCR should be considered first, followed by additional NGS testing


Biomarker testing provides more insight into the pathophysiology of mG/GEJ cancer as more biomarkers are discovered.

  • Standard IHC staining methods can detect a wide range of investigational and known biomarkers

    • IHC can detect CLDN18.2, FGFR2b, PD-L1, HER2, MMR6,8,11
    • Other testing methods often focus on specific biomarkers (ctDNA for FGFR2, ISH/NGS for HER2,* and PCR/NGS for MSI)6,15,16

      • * IHC/ISH should be considered first, followed by additional NGS testing as appropriate.6

  • In various international clinical trials, biomarker testing has revealed a high prevalence of investigational biomarkers

    • 29% of primary gastric cancers and 34% of nodal metastases were CLDN18.2 positive (high expression)8
    • 3–61% of gastric cancers demonstrate FGFR2b overexpression18
  • Prevalence of known biomarkers have been reported throughout international clinical trials as:

    • HER2 positivity in 22% of advanced mG/GEJ cancers12
    • MSI-H in 4% of mG/GEJ cancers21
    • PD-L1 at several positivity thresholds: 67–73% CPS ≥1, 29–31% CPS ≥5, and 16–18% CPS ≥1019,20



As biomarker research continues, it expands our view of the patient population and reveals more information about the pathophysiology of mG/GEJ cancer.

Astellas Answers logo.



Have a question?
 

ASK OUR MEDICAL INFORMATION TEAM

Download a PDF about the biomarker advancements in mG/GEJ cancers.

DOWNLOAD PDF

REFERENCES

  1. Statistics Canada. Table 13-10-0160-01. Age-standardized five-year net survival estimates for primary sites of cancer, by sex, three years combined. November 27, 2020. https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310016001. Accessed 11-10-2022.
  2. Canadian Cancer Statistics Advisory Committee in collaboration with the Canadian Cancer Society, Statistics Canada and the Public Health Agency of Canada. Canadian Cancer Statistics 2021. Toronto, ON: Canadian Cancer Society; 2021.
  3. Brenner DR, Poirier A, Woods RR, et al. Projected estimates of cancer in Canada in 2022. CMAJ 2022;194:E601–607.
  4. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin 2021;71(3):209–49.
  5. Casamayor M, Morlock R, Maeda H, Ajani J. Targeted literature review of the global burden of gastric cancer. Ecancermedicalscience. 2018;12:883.
  6. NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer. Version 2.2022.
  7. Günzel D, Yu ASL. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013;93(2):525–569.
  8. Coati I, Lotz G, Fanelli GN, et al. Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. Br J Cancer. 2019;121(3):257–263.
  9. Li J, Zhang Y, Hu D, Gong T, Xu R, Gao J. Analysis of the expression and genetic alteration of CLDN18 in gastric cancer. Aging (Albany NY). 2020;12(14):14271–14284.
  10. Matsuoka T, Yashiro M. Biomarkers of gastric cancer: Current topics and future perspective. World J Gastroenterol. 2018;24(26):2818–2832.
  11. Ahn S, Lee J, Hong M, et al. FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol. 2016;29(9):1095–1103.
  12. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476–484.
  13. Baudrin LG, Deleuze JF, How-Kit A. Molecular and computational methods for the detection of microsatellite instability in cancer. Front Oncol. 2018;8:621.
  14. Kawazoe A, Shitara K, Kuboki Y, et al. Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer. 2019;22(1):69–76.
  15. Jogo T, Nakamura Y, Shitara K, et al. Circulating Tumor DNA Analysis Detects FGFR2 Amplification and Concurrent Genomic Alterations Associated with FGFR Inhibitor Efficacy in Advanced Gastric Cancer. Clin Cancer Res. 2021;27(20):5619–5627.
  16. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol. 2016;22(19):4619–4625.
  17. Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41(10):868–876.
  18. Kim HS, Kim JH, Jang HJ, et al. Pathological and Prognostic Impacts of FGFR2 Overexpression in Gastric Cancer: A Meta-Analysis. J Cancer. 2019 Jan 1;10(1):20–27.
  19. Schoemig-Markiefka B, Eschbach J, Scheel AH, et al. Optimized PD-L1 scoring of gastric cancer. Gastric Cancer. 2021;24(5):1115–1122.
  20. Fuchs CS, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022;25(1):197–206.
  21. Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4(5):e180013. Erratum in: JAMA Oncol. 2019;5(4):579.
  22. Niimi T, Nagashima K, Ward JM, et al. Claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing. Mol Cell Biol. 2001;21(21):7380–7390.
  23. Li WT, Jeng YM, and Yang CY. Claudin-18 as a Marker for Identifying the Stomach and Pancreatobiliary Tract as the Primary Sites of Metastatic Adenocarcinoma. Am J Surg Pathol. 2020;44(12):1643–1648.
  24. Kurban G, Ishiwata T, Kudo M, Yokoyama M, Sugisaki Y, Naito Z. Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in human uterine cervical cancer. Oncol Rep. 2004;11(5):987–991.
  25. Szybowska P, Kostas M, Wesche J, et al. Cancer Mutations in FGFR2 Prevent a Negative Feedback Loop Mediated by the ERK1/2 Pathway. Cells. 2019;8(6):518.
  26. National Cancer Institute. NCI dictionary of cancer terms: TNM staging system. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tnm-staging-system. Accessed 10-04-2022.
  27. Vicario R, Peg V, Morancho B, et al. Patterns of HER2 gene amplification and response to anti-HER2 therapies. PLoS One. 2015;10(6):e0129876.
  28. Wu Y, Chen W, Xu ZP, Gu W. PD-L1 distribution and perspective for cancer immunotherapy-blockade, knockdown, or inhibition. Front Immunol. 2019;10:2022.
  29. Qing Y, Li Q, Ren T, et al. Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer. Drug Des Devel Ther. 2015;9:901–909.
  30. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27–40.



BACK

Terms of Use

The information provided on gastriccancerbiomarkers.ca is intended for residents of Canada.
© 2023 Astellas Pharma Canada, Inc. All rights reserved.

WEBSITE TERMS OF USE (Effective date: 04/23)

 

ATTENTION: PLEASE READ THESE TERMS CAREFULLY BEFORE USING THIS WEBSITE GASTRICCANCERBIOMARKERS.CA. BY USING THIS SITE, INCLUDING ANY SERVICES PROVIDED ON OR THROUGH THIS SITE GASTRICCANCERBIOMARKERS.CA (“Services”), YOU INDICATE THAT YOU ACCEPT THESE TERMS. IF YOU DO NOT ACCEPT THESE TERMS, DO NOT USE THIS SITE.

 

Astellas Pharma Canada, Inc., (Astellas) may at any time revise these Terms of Use by updating this posting, so you should periodically examine the current Terms of Use to which you are bound. Certain provisions of these Terms of Use may be superseded by expressly designated legal notices or terms located on particular pages at this Site. To view the Terms of Use at any time, go to GastricCancerBiomarkers.ca.

GENERAL INFORMATION. This Site contains information that may be of interest to members of the healthcare community. Please feel free to browse this Site and Services. Your access and use of the Site are subject to the following terms and conditions, and all applicable laws. By accessing and browsing this Site and Services, you accept, without limitation or qualification, these terms and conditions and acknowledge that they supersede any other agreement between you and Astellas.

PRIVACY. Astellas policies concerning the use of your personal information are set forth in Astellas's Privacy Policy, which you can find by clicking here, and which are incorporated by reference herein. By using this Site or any services provided by or through this Site (Services), you agree to waive and release Astellas from any claim or liability in connection with the collection, use, or disclosure of information consistent with Astellas's Privacy Policy.

SITE CONTENT. All material on the Site including, but not limited to, text, images, graphics, documents, audio, or video (collectively, the Site Content) are protected under applicable copyright laws. You may copy, download, or print Site Content for your personal, noncommercial purposes only, but no modification or further reproduction of content is permitted. The Site Content may not otherwise be copied, downloaded, reproduced, deleted, modified, republished, retransmitted, displayed, or used to create derivative works without the express written permission of Astellas.

Trademarks, service marks, trade dress, logos, designs, and slogans appearing on this Site are owned by Astellas, its Affiliate companies, its licensors, or its partners, and may not be used for advertising or publicity purposes, or to indicate any affiliation with or endorsement by Astellas, except with the express written permission of Astellas.

Nothing contained in this Site should be construed as granting a licence to, or right in, any trademarks, patents, or copyrights of Astellas, or any other party.

You are solely responsible for any content, including but not limited to text, photographs, caricatures, illustrations, designs, icons, articles, audio clips, and video clips (collectively, User Content) that you post, email, or otherwise transmit via this Site. Astellas does not own or endorse User Content posted or otherwise transmitted via this Site, and Astellas does not guarantee the accuracy, integrity, or quality of such User Content. Any communications you send via this Site or otherwise to Astellas by email, with the exception of personally identifiable information as defined in Astellas' Privacy Policy, shall be deemed to be nonconfidential and Astellas shall have no obligation of any kind with respect to such information and shall be free to reproduce, use, disclose, and distribute the information to others without limitation. Astellas shall be free to use any ideas, concepts, know-how, or techniques contained in such information for any purpose whatsoever, including but not limited to developing, manufacturing, and marketing activities incorporating such information.

The content or material Astellas provides through the Site is for informational purposes only. Nothing on this Site should be construed as the giving of advice (medical, legal, financial, investment, or other professional advice) or the making of a recommendation, and information on the Site should not be relied on as the basis for any decision or action. This Site is not intended to promote any product or treatment, or to impact or influence any purchasing, prescribing or diagnosis decisions.

OBLIGATIONS OF SITE VISITORS OR USERS. You agree not to do any of the following while visiting or using the Site or any services provided by or through this Site:

  • Impersonate or misrepresent your affiliation with any person or entity;
  • Except as expressly permitted by the rules of this Site, post or transmit any unsolicited advertising, promotional materials, (junk mail), (spam), (chain letters), or any other form of solicitation on the Site or through the Services;
  • Post or transmit any information or material that is defamatory, offensive, indecent, obscene, or unlawful;
  • Post or transmit any information or software which contains a virus, Trojan horse, worm, or other harmful components;
  • Violate any applicable law or regulation, including without limitation any local, state, provincial, national or international law, any export control laws, or any regulations promulgated by any state or federal authority;
  • Access or use password-protected, secure or nonpublic areas of the Site without authorization; or
  • Frame, repackage, or otherwise redistribute any portion of the Site.

Astellas may, in its sole discretion, take any action it deems necessary, including but not limited to termination of access to the Site or modification of User Content, if Astellas believes a user's conduct or content fails to conform to these Terms of Use or may create liability for Astellas, its partners, its suppliers, or any other party or person. Astellas will not be liable to you or any third party as a result of such termination or modification. The terms and conditions provided in these Terms of Use will survive any such termination and modification.

LINKS TO OTHER WEBSITES. Solely as a convenience to you, Astellas may provide links on this Site to other websites that are not maintained by or under the control of Astellas. If you use these links, you will leave this Site. Please remember that linked sites are not necessarily Astellas's sites, and the information could change without Astellas's knowledge. Third-party linked sites and their contents should not be attributed to Astellas (or any of its affiliated companies) in any manner. Astellas has not attempted to verify the truth or accuracy of any third-party sites or content contained on any third-party sites and does not make any representations or warranties about such sites or the content of such sites. If you decide to access any of the third-party sites linked to this Site, you do so entirely at your own risk. In the event Astellas endorses a particular organization, Astellas will clearly state its endorsement next to any link to that organization.

DISCLAIMER OF WARRANTIES. THIS SITE, INCLUDING ANY INFORMATION, SERVICES, OR MATERIAL MADE AVAILABLE ON OR THROUGH THIS SITE, IS PROVIDED ON AN "AS IS" AND "AS AVAILABLE" BASIS. TO THE MAXIMUM EXTENT PERMITTED BY LAW, ASTELLAS EXPRESSLY DISCLAIMS ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY WARRANTY OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, OR NONINFRINGEMENT. FURTHERMORE, ASTELLAS DOES NOT WARRANT THE ACCURACY OR COMPLETENESS OF ANY INFORMATION ON THIS SITE AND MAY MAKE CHANGES TO THE INFORMATION, SERVICES, OR MATERIAL MADE AVAILABLE ON OR THROUGH THIS SITE AT ANY TIME WITHOUT PRIOR NOTICE TO USERS OF THIS SITE. INFORMATION AT THIS SITE THAT IS PERIODICALLY UPDATED MAY NOT BE CURRENT AT THE MOMENT YOU VISIT THIS SITE AND MAY CONTAIN ERRORS. ASTELLAS MAKES NO WARRANTY THAT THE SITE WILL MEET YOUR REQUIREMENTS; THAT THE SITE WILL BE UNINTERRUPTED, TIMELY, SECURE, OR ERROR-FREE; THAT MESSAGES OR REQUESTS WILL BE DELIVERED; THAT DEFECTS WILL BE CORRECTED; OR THAT THIS SITE IS FREE OF VIRUSES OR OTHER HARMFUL COMPONENTS. ASTELLAS MAKES NO WARRANTY REGARDING ANY GOODS OR SERVICES PURCHASED OR OBTAINED THROUGH THE SITE OR ANY TRANSACTIONS ENTERED INTO THROUGH THE SITE. YOU ASSUME THE ENTIRE RISK AS TO THE RESULTS AND PERFORMANCE OF THE SITE AND ANY GOODS OR SERVICES PURCHASED THEREFROM.

LIMITATION OF LIABILITY. IN NO EVENT WILL ASTELLAS BE LIABLE FOR ANY DAMAGES WHATSOEVER. THIS INCLUDES BUT IS NOT LIMITED TO DIRECT, INDIRECT, INCIDENTAL, PUNITIVE, AND CONSEQUENTIAL DAMAGES (INCLUDING, WITHOUT LIMITATION, THOSE RESULTING FROM LOST PROFITS, LOST DATA, OR BUSINESS INTERRUPTION) ARISING OUT OF THE USE, INABILITY TO USE, OR THE RESULT OF USE OF THIS SITE, ANY WEBSITES LINKED TO THIS SITE, THE MATERIALS OR INFORMATION CONTAINED ON ANY OR ALL SUCH SITES, OR ANY MATERIALS, PRODUCTS, OR SERVICES OFFERED ON THIS SITE OR SITES LINKED TO THIS SITE, WHETHER BASED ON WARRANTY, CONTRACT, TORT, OR ANY OTHER LEGAL THEORY AND WHETHER OR NOT ADVISED ON THE POSSIBILITY OF SUCH DAMAGES. IN NO EVENT WILL ASTELLAS, ITS SUPPLIERS, OR ANY OTHER PARTY INVOLVED IN CREATING, PRODUCING, OR DELIVERING THIS SITE BE LIABLE TO YOU IN ANY MANNER WHATSOEVER FOR ANY DECISION MADE OR ACTION OR NONACTION TAKEN BY YOU IN RELIANCE UPON INFORMATION PROVIDED THROUGH THIS SITE. APPLICABLE LAW MAY NOT ALLOW THE EXCLUSION OR LIMITATION OF INCIDENTAL OR CONSEQUENTIAL DAMAGES, SO THE ABOVE LIMITATION OR EXCLUSION MAY NOT APPLY TO YOU.

THIS SITE IS INTENDED FOR CANADIAN AUDIENCES ONLY.  Access to and use of this Site is subject to the above terms and conditions. This Site was developed and is maintained by Astellas. Information, copy, and claims are intended only for the residents of Canada.