Current and future applications of biomarkers in samples collected through minimally invasive methods for cancer medicine and population-based research

Abstract

Despite advances in cancer medicine and research, invasive and potentially risky procedures such as biopsies, venous blood tests, imaging, colonoscopy, and pap smear tests are still primarily used for screening, staging, and assessing response to therapy. The development and interdisciplinary use of biomarkers from urine, feces, saliva, scent, and capillary blood collected with minimally invasive methods represents a potential opportunity for integration with biomarker analysis for cancers, both in clinical practice (e.g., in screening, treatment, and disease monitoring, and improved quality of life for patients) and population-based research (e.g., in epidemiology/public health, studies of social and environmental determinants, and evolutionary medicine). In this article, we review the scientific rationale, benefits, challenges, and potential opportunities for measuring cancer-related biomarkers in samples collected through minimally invasive methods.

FIGURE 1

Common cellular pathways detected with cancer biomarkers. Green endpoints are primarily cancer-preventing, and yellow endpoints are primarily cancer-promoting. Expression of many of the biomarkers listed above can be detected at the mRNA or protein levels. Some, such as EGFR are pictured here as genes and proteins, whereas others such as CDKN2A (associated with the protein p16) are only depicted as one or the other. 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, 5-hydroxytryptamine (serotonin); PSA, prostate specific antigen; PCA3, Prostate cancer antigen 3; BTA, bladder tumor antigen; VMA, vanillylmandelic acid; HMA, homomandelic acid; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor; RAS and KRAS, rat sarcoma associated proteins; CDKN2a, cyclin dependent kinase inhibitor 2a; BCRP, breast cancer resistance protein; RAF, rapidly accelerated fibrosarcoma protein kinases; MEK, mitogen activated protein kinase; ERK, extracellular signal-regulated kinase; PTEN, phosphatase and tensin homolog; PK-13, protein kinase 13; MTOR, mechanistic target of rapamycin; FOXO, forkhead family of transcription factors. Created with Biorender.com

FIGURE 2

Multilevel structure of human cancer biology. The levels presented were adapted from Novikoff, 1945. This structure should be controlled for statistically using a multilevel model or including group-level control variables