Table 2

Strategies for treatment and prevention of IEN in major cancer target organs

Target organCohorts for clinical studiesPrimary endpointsEarly associated biomarkers
Colon/rectumPrevious adenomasPrevention of adenomasACF, proliferation antigens (PCNA, Ki-67), apoptosis, differentiation antigens (Lewisx, Lewisy, T, Tn, and sialyl-Tn antigens and apomucins), K-ras, DNA methylation
FAPRegression and prevention of adenomas
Head and neckAdolescent FAP (prephenotype expression)Prevention of adenomas
OPLs (atypical hyperplasia, hyperkeratosis, mild to severe dysplasia)Regression of existing OPL and/or prevention of new OPLLOH (3p, 9p), p53, cyclin D1, growth factors (e.g., EGFR), retinoid receptors (RARβ), DNA content, proliferation antigens (PCNA, Ki-67), apoptosis
Esophagus (adenocarcinoma)Barrett’s esophagus (mild to severe dysplasia)Regression and/or slowed progression of Barrett’s dysplasiaDNA contents, proliferation antigens (PCNA, Ki-67), ODC, growth factors (e.g., EGFR), cyclin D1, p16, p53, Cdx1 and Cdx2
CervixHGSIL (CIN 2/3)Regression and prevention of CINLOH (3p, 4p, 4q, 11q), proliferation antigens (PCNA), growth factors (e.g., EGFR), K-ras, differentiation antigens
LungBronchial dysplasia (current or former smokers)Regression and prevention of bronchial dysplasiaProliferation antigens (Ki-67), LOH (3p, 8p, 9p), K-ras, retinoid receptors, p53, FHIT, DNA methylation, apoptosis
Skin (nonmelanoma)Transplant patients (with previous nonmelanoma skin cancer)Prevention of skin SCC (and, as a secondary endpoint, of AK)Proliferation antigens (PCNA), ODC, growth factors (e.g., EGFR, TGFβ), p53
High-risk AK (>10 AK within previous year)Prevention of AK (and, as a secondary endpoint, of skin SCC and, as a tertiary endpoint, regression of AK)
BreastHyperplasia without atypiaPrevention of atypical hyperplasiaDNA methylation, LOH, growth factors (e.g., EGFR, erbB-2, IGF), proliferation antigens (Ki-67, PCNA), p53, apoptosis
Atypical hyperplasiaRegression of atypical hyperplasia
ProstateHGPIN without cancerRegression of HGPINDNA methylation, GST, pc-1 chromosomal loss or gain (8p, 9p, 16q), apoptosis, proliferation antigens (Ki-67), growth factors (IGF, TGF-α, TGF-β)
Prevention of prostatic carcinoma
BladderTa, T1 superficial bladder cancer (papillary TCC)Prevention of new superficial cancers and of progression (incidence or time to event)LOH (3p, 9p, 11p, 17p, 18q), p53, proliferation antigens (Ki-67, PCNA, M344), differentiation antigens (γ-actin), growth factors (e.g., EGFR), autocrine motility factor receptor
Ta, T1 ± TIS superficial bladder cancer (after BCG treatment)