Systemic Therapies in Metastatic Non-Small-Cell Lung Cancer with Emphasis on Targeted Therapies: The Rational Approach

Abstract

The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, plays an important role in the control of cell growth and differentiation. Disruption of its signaling leads to neoplastic cell proliferation, migration, stromal invasion, resistance to apoptosis, and angiogenesis.EGFR is overexpressed in a variety of solid tumors, including colorectal cancer (CRC), and its overexpression is associated with poorer prognosis. One class of agents that is currently used to target EGFR in the treatment of metastatic CRC (mCRC) is the monoclonal antibodies. While the monoclonal antibody EGFR inhibitors lack many of the severe side effects commonly observed with cytotoxic chemotherapy, they are associated with a set of unique dermatological toxicities. This paper reviews the safety profile of the anti-EGFR monoclonal antibodies cetuximab and panitumumab in the treatment of mCRC. KEY WORDSepidermal growth factor receptor, skin toxicity, cetuximab, panitumumab

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

“…Thus, all pathways that this gene regulates are functioning normally or if activated, this activation is not induced by EGFR. 41,57,58 Papillary pattern proliferation properties could in part be explained by APC upregulation when compared to normal tissue.…”

Anti-EGFR Antibody Cetuximab Enhances the Cytolytic Activity of Natural Killer Cells toward Osteosarcoma

“…The chemotherapy-resistant variant cell lines of SAOS-2 and U2-OS (16)(17)(18) were cultured in IMDM medium with 10% FCS and penicillin/streptomycin and maintained in chemotherapeutic drugs as follows: SAOS-2-DX580 and U2-OS-DX580 with 580 mg/mL of doxorubicin (DX); SAOS-2-MTX1000 and U2-OS-MTX300 with 1,000 and 300 ng/mL of methotrexate (MTX), respectively; SAOS-2-CDDP6 (SAOS-2-CDDP6mg) and U2-OS-CDDP4 (U2-OS-CDDP4ug) with 6 and 4 mg/mL of cisplatin (cis-diamminedichloroplatinum, CDDP), respectively. Drug sensitivities of each cell line were calculated from the drug dose-response curves and expressed as IC 50 (drug concentration resulting in 50% inhibition of cell growth after 96 hours of in vitro treatment). Fold increases in drug resistance, quantified as the ratio between IC 50 of each drug-resistant variant to that of its corresponding parental cell line, were as follows: 315 for U2-OS-DX580, 328 for SAOS-2-DX580, 135 for U2-OS-MTX300, 281 for SAOS-2-MTX1mg, 63 for U2-OS-CDDP4mg, and 112 for SAOS-2-CDDP6mg.…”

Assessment of frequency and severity of hypomagnesemia in patients with metastatic colorectal cancer treated with cetuximab, with a review of the literature

“…Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with an intracellular component that acts as a tyrosine kinase (1). As the EGFR/K-ras pathway is commonly activated in metastatic colorectal cancer (mCRC), it is an attractive target for molecular therapy (1).…”

“…As the EGFR/K-ras pathway is commonly activated in metastatic colorectal cancer (mCRC), it is an attractive target for molecular therapy (1).…”

“…The CO.17 trial proved that cetuximab monotherapy administered following progression on chemotherapy lines (oxaliplatin and irinotecan with 5-fluorouracil) also improves OS, PFS and ORR (5). Inhibition of the EGFR/K-ras pathway by cetuximab is connected with numerous side-effects, such as skin toxicity, diarrhea, hypomagnesemia and other dyselectrolytemias or infusion reactions (1,7). A previous study by our group (7) analyzed skin toxicity associated with cetuximab-based therapy; acnelike rash was observed at a frequency of 80% and paronychia at 20%.…”