br de la Puente P
160. de la Puente P, Luderer MJ, Federico C, et al. Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma. Journal of controlled release : official journal of the Controlled Release Society. Jan 28 2018;270:158-176.
162. Huang YH, Vakili MR, Molavi O, et al. Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma. Cancers. Feb 20 2019;11(2).
Table 1: Targeted Nanomedicines for Cell Type-Specific Delivery
Cell-Type Targeted Targeted Receptor Targeting Moiety Examples
Tumor PSMA Antibody 30-32
Cells/Endothelium EGFR Peptide 26-28
Folate Receptor Folate 141,142
P-selectin Fucoidan 41
CD44 Antibody 36
M2 Tumor Associated Mannose Receptor Monosaccharide 102,109
Sialic Acid Receptor Sialic Acid 111
SR-B1 Receptor Apo-1 Peptide 144
Th2 Regulatory T-cells GITR Peptide 112,113
Nrp1 Peptide 145
Tumor-Associated Sigma-Receptor Anisamide 118-120
Dendritic Cells SR-B1 Receptor Peptide 144
T-Lymphocytes CD3 Antibody 146,147
CD4 Antibody 148
B-Lymphocytes/Plasma CD19 Antibody 151-154
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Biomarker concordance between primary colorectal cancer and its metastases
Colorectal & Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
Division of Cancer Sciences, School of Medical Science, Faculty of Biology, Medicine and Health, University of Manchester, UK
Background: The use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer (CRC) 9064-57-7 well-established, requiring molecular analysis of primary or metastatic biopsies. We aim to review concordance between primary CRC and its metastatic sites.
Methods: A systematic review and meta-analysis of all published studies (1991–2018) reporting on biomarker concordance between primary CRC and its metastatic site(s) was undertaken according to PRISMA guidelines using several medical databases. Studies without matched samples or using peripheral blood for biomarker anal-ysis were excluded.
© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Advances in biological therapies such as anti-epidermal growth factor receptor (EGFR) antibodies (cetuximab and panitumumab) have resulted in biomarkers being used to target metastatic CRC (mCRC) . KRAS is a key proto-oncogene downstream of EGFR and is activated in up to 50% of sporadic mCRC patients, with 95% of activa-tions occurring in codons 12/13 of exon 2 . Importantly, KRAS exon
Corresponding author at: Consultant Colorectal Surgeon, Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.
E-mail address: [email protected] (O. Aziz).
1 Signifies co-first authors.
2–4 mutations (involving codons 12, 13, 161, 117 & 146) demonstrate a significantly lower response to cetuximab and panitumumab [13,14]. Some studies have also indicated that KRAS mutations may confer resis-tance to bevacizumab [15,16]. The extended RAS family of oncogenes includes NRAS, with exon 2–4 mutations occurring in 3–5% of CRC's and similarly resulting in a lower response [17,18]. BRAF, a RAF gene kinase and immediate downstream effector of KRAS, shows mutations in nearly 10% of colorectal adenocarcinomas and is also a strong nega-tive prognostic marker, predicting resistance to both cytotoxic and anti-EGFR therapy [19–21].
Mutations in genes other than those constituting the RAS/RAF path-way include PIK3CA and PTEN . Approximately 15–20% of patients with mCRC, have mutations in exon 20 of PIK3CA and demonstrate resistance to cetuximab even in the presence of KRAS wild type . Loss of expression of PTEN, a natural inhibitor of PI3K-initiated signal-ling, has itself also been associated with unresponsiveness to cetuximab and reduced OS [24,25]. Beyond the factors associated with EGFR signal-ling pathways, a number of other genes are significantly mutated in CRC, including APC (51–81%), TP53 (20–60%), and SMAD4 (10–20%) . APC is the most prevalent gene in the establishment of sporadic co-lorectal malignancy . Similar to APC, the TP53 gene is heavily