Translational Biomarkers: Application in the Clinical Development of Combination Therapies

  • Selvakumar Sukumar
  • Niña G. Caculitan


Development of appropriate pharmacodynamic and safety markers early in drug development can result in a higher probability of success for new drug candidates. As the overarching goal of cancer therapy is to effectively eradicate cancer in a manner that is tolerable and safe for use in the intended patient population, application of biomarkers can facilitate effective patient selection with a positive impact on the final therapeutic outcome. Additionally, combination therapies for the treatment of cancer have emerged as an effective way to anticipate and overcome cancer heterogeneity and resistance. With the emergence of cancer immune oncology (IO), clinical trials for the combination of traditional oncology drugs and immune checkpoint blockade are ongoing. The discussions in this chapter are focused on the use of current and emergent biomarkers in the design and development of treatment combinations for cancer, with a special emphasis on emerging IO therapies.



Biotechnology innovation orgaization


College of American Pathologists


Clinical Laboratory Improvement Amendments


Companion diagnostics


Food and Drug Administration


Formalin fixed paraformaldehyde embedded


First-in-human dose


Gene expression profile


Good laboratory practice


Hematoxylin and eosin


Human equivalent dose


Human leukocyte antigen


Immunohistochemistry test




Immune-related adverse events


Minimally anticipated biological effect level


Major histocompatibility complex


DNA mismatch repair


Mechanism of action


Nonhuman primates


No observed adverse effect level


Non-small cell lung cancer


Peripheral blood mononuclear cells




Progression-free survival


Proof of concept


Proof of mechanism


Receptor occupancy


T-cell receptor


Tumor proportion score


Treatment-related adverse events


Vascular endothelial growth factor


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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Selvakumar Sukumar
    • 1
  • Niña G. Caculitan
    • 2
  1. 1.CSL BehringKing of PrussiaUSA
  2. 2.Gritstone OncologyEmeryvilleUSA

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