Cetuximab for treating non-small cell lung cancer

Abstract

Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.

Clathrin‐mediated EGFR endocytosis as a potential therapeutic strategy for overcoming primary resistance of EGFR TKI in wild‐type EGFR non‐small cell lung cancer

“…The mAbs, such as cetuximab, have been approved as a treatment for progressive colorectal cancer patients, as well as head and neck cancer patients 13,14 . However, cetuximab currently has no role in treatment of NSCLC patients, because of its marginal clinical benefit 15 . Gefitinib is the first EGFR TKI approved for clinical use in lung cancer patients.…”

“…13,14 However, cetuximab currently has no role in treatment of NSCLC patients, because of its marginal clinical benefit. 15 Gefitinib is the first EGFR TKI approved for clinical use in lung cancer patients. EGFR TKIs have been recommended as a potential first-line treatment for advanced NSCLC patients with somatic EGFR TK domain mutations such as exon 19 deletions (E746-A750 (2235-2249del), E746-A750 (2236-2250del), L747-E749 A750P (2239-2247 and 2248del), etc.…”

Mutation detection and molecular targeted tumor therapies

“…Molecular targeted therapy (MTT) is a research hotspot in the field of cancer therapy in recent years. It has been characterized by high efficiency and low toxicity in the treatment of gastrointestinal stromal tumors, lymphoma, breast cancer, colorectal cancer, and non-small cell lung cancer (34)(35)(36)(37)(38). It targets some of the iconic molecules overexpressed in tumor cells, and selects targeted blocking agents to effectively interfere with the signaling pathways closely related to tumorigenesis, thereby inhibiting tumor growth, progression and metastasis (39).…”

The anthelmintic agent oxfendazole inhibits cell growth in non‑small cell lung cancer by suppressing c‑Src activation

“…Non-small cell lung cancer (NSCLC) is one of the most common malignancies, accounting for 85% of all lung cancer cases, and its treatment continues to be severe challenge in the clinic (1). Although significant progress has been made in regard to drug development, there are still few drugs that have long-term benefits in the treatment of NSCLC (2)(3)(4). Therefore, there is an urgent demand to identify novel targets and drugs to improve systemic therapy for patients with NSCLC.…”