Focus on HER1

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Focus on HER1
Slide kit provided by ResearchHERpathways.com, an
online resource sponsored by Genentech
BioOncology.
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HER1/EGFR may play an important role in the
development of cancer
...there is an important role for aberrant EGFR
signaling in the development and progression of
various human tumors. Herbst RS and Bunn PA
Jr, Clin Cancer Res, 20031
Reference 1. Herbst RS, Bunn PA Jr. Clin Cancer
Res. 200395813-5824.
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Focus on HER1 dysregulation
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HER1/EGFR dysregulation has multiple effects on
cancer cells

• The downstream signaling pathways initiated by
  activation of HER1/EGFR dimers have numerous
  effects on cancer cells, enabling them to grow
  and spread1

Reference 1. Herbst RS, Bunn PA Jr. Clin Cancer
Res. 200395813-5824.
Adapted from Herbst et al, Clinical Cancer
Research, 2003. Reprinted with permission from
the American Association for Cancer Research.
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Focus on HER1/EGFR evaluation
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There are different ways of evaluating HER1/EGFR

• HER1/EGFR can be detected in a number of
  different ways, including genomic and proteomic
  assays1

Reference 1. Sonnweber B, Dlaska M, Skvortsov S,
et al. J Clin Pathol. 200659255-259.
Reprinted from Sonnweber et al, J Clin Pathol.
200659255-259.
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Focus on HER1/EGFR and prognosis
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HER1/EGFR overexpression has been correlated with
shorter overall survival in early-stage NSCLC
Selvaggi G et al. Epidermal growth factor
receptor overexpression correlates with a poor
prognosis in completely resected non-small-cell
lung cancer. Annals of Oncology. 20041528-32.
By permission of the European Society for Medical
Oncology.
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Focus on HER1/EGFR in lung and pancreatic cancer
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Prevalence of HER1/EGFR overexpression in NSCLC
in various clinical studies
References 1. Onn A, Correa AM, Gilcrease M, et
al. Clin Cancer Res. 200410136-143. 2. Rusch V,
Baselga J, Cordon-Cardo C, et al. Cancer Res.
1993532379-2385. 3. Selvaggi G, Novello S,
Torri V, et al. Ann Oncol. 20041528-32. 4.
Ohtsuka K, Ohnishi H, Furuyashiki G, et al. J
Thorac Oncol. 20061787-795.
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Prevalence of HER1/EGFR overexpression/amplificati
on in pancreatic cancer in various clinical
studies

• Clinical studies indicate that pancreatic cancers
  overexpress HER1/EGFR and may carry
  amplifications of the EGFR gene

References 1. Dancer J, Takei H, Ro JY,
Lowery-Nordberg M. Oncol Rep. 200718151-155. 2.
Bloomston M, Bhardwaj A, Ellison EC, Frankel WL.
Dig Surg. 20062374-79. 3. Thybusch-Bernhardt A,
Beckmann S, Juhl H. Int J Surg Investig.
20012393-400.
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Focus on HER1/EGFR as a therapeutic target
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Strategies for targeting HER1/EGFR

• HER1/EGFR contains both an extracellular
  ligand-binding domain and an intracellular
  tyrosine kinase domain, which is activated to
  initiate multiple downstream signaling
  pathways.1-3 Therefore, HER1/EGFR can be targeted
  in several ways

References 1. Ettinger DS. Oncologist.
200611358-373. 2. Prenzel N, Fischer OM,
Streit S, et al. Endocr Relat Cancer.
2001811-31. 3. Sliwkowski MX. In Harris JR,
Lippman ME, Morrow M, Osborne CK, eds. Diseases
of the Breast. 3rd ed. Philadelphia, PA
Lippincott Williams Wilkins 2004415-426.
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Focus on HER1/EGFR in cancer Summary
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HER1/EGFR represents a potential therapeutic
target

• HER1/EGFR signaling is frequently dysregulated in
  cancer1-4
• HER1/EGFR is a negative prognostic factor5-8
• Methods of targeting could include
• Targeting HER1/EGFR-specific ligands
• Targeting the ligand-binding domain of HER1/EGFR
• Targeting the tyrosine kinase domain of the
  receptor
• Targeting downstream signaling pathways
• Additional clinical research is needed to better
  clarify the role of HER1/EGFR in cancer

References 1. Prenzel N, Fischer OM, Streit S,
et al. Endocr Relat Cancer. 2001811-31. 2.
Fujino S, Enokibori T, Tezuka N, et al. Eur J
Cancer. 199632A2070-2074. 3. Rusch V, Baselga
J, Cordon-Cardo C, et al. Cancer Res.
1993532379-2385. 4. Herbst RS, Bunn PA Jr. Clin
Cancer Res. 200395813-5824. 5. Selvaggi G,
Novello S, Torri V, et al. Ann Oncol.
20041528-32. 6. Kanematsu T, Yano S, Uehara H,
et al. Oncol Res. 200313289-298. 7. Ueda S,
Ogata S, Tsuda H, et al. Pancreas. 200429e1-e8.
8. Yamanaka Y, Friess H, Kobrin MS, et al.
Anticancer Res. 199313565-570.