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Using extracellular biomarkers for monitoring efficacy of therapeutics in cancer patients: an update

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Abstract

Rapidly detectable and easily accessible markers of tumor cell death are needed for evaluating early therapeutic efficacy for immunotherapy and chemotherapy so that patients and their physicians can decide whether to remain with a given therapeutic strategy. Currently, image-based tests such as computed tomography scans and magnetic resonance imaging are used to visualize the response of a patient’s tumor, but often these evaluations are not conducted for weeks to months after treatment begins. While serum levels of secreted proteins such as carcinoembryonic antigen and prostate specific antigen are commonly monitored to gauge tumor status during therapy and between image evaluations, the levels of these proteins do not always correlate well with the actual tumor response. In laboratory studies, it has been shown that tumor cells undergoing apoptosis can release cellular components into cell culture media such as cytochrome c, nucleosomes, cleaved cytokeratin-18 and E-cadherin. Studies of patient sera have found that these and other macromolecules can be found in circulation during cancer therapy, providing a potential source of material for monitoring treatment efficacy. In the future, analysis of biofluids from severe combined immunodeficiency mice bearing patient tumor specimens treated with a targeted therapy such as Apo2L/tumor necrosis factor-related apoptosis-inducing ligand will be useful in the preclinical identification of therapy response markers. In this review, the current status of the identification of serum markers of tumor cell apoptosis is provided, as well as a discussion of critical research questions that must be addressed and the considerations necessary when identifying a marker that reflects true clinical outcome.

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Abbreviations

CEA:

Carcinoembryonic antigen

CK18:

Cytokeratin-18

CT:

Computed tomography

DISC:

Death-inducing signaling complex

EGFR:

Epithelial growth factor receptor

FADD:

Fas-associated death domain

FDG:

18F-deoxyglucose

FLT:

18F-fluorothymidine

LDH:

Lactate dehydrogenase

MMP:

Matrix metalloproteinase

MRI:

Magnetic resonance imaging

NCCN:

National comprehensive cancer network

PDT:

Photodynamic therapy

PET:

Positron emission tomography

PSA:

Prostate specific antigen

RECIST:

Response evaluation criteria in solid tumors

SEER:

Surveillance epidemiology and end results

SCID:

Severe combined immunodeficiency

SPECT:

Single photon emission computerized tomography

TIMP:

Tissue inhibitor of MMPs

TNF:

Tumor necrosis factor

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

TUNEL:

Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling

WHO:

World Health Organization

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  1. Department of Molecular and Cellular Biophysics and Biochemistry, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    S. H. Beachy

  2. Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    E. A. Repasky

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  1. S. H. Beachy
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Beachy, S.H., Repasky, E.A. Using extracellular biomarkers for monitoring efficacy of therapeutics in cancer patients: an update. Cancer Immunol Immunother 57, 759–775 (2008). https://doi.org/10.1007/s00262-007-0445-6

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  • DOI: https://doi.org/10.1007/s00262-007-0445-6

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