Current Trends of Drugs Acting on Oral Squamous Cell Carcinoma (OSCC)
Prakash Srinivasan Timiri Shanmugam in Understanding Cancer Therapies, 2018
Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used for the treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head and neck cancer (HNC). Cetuximab is a chimeric (mouse/human) monoclonal antibody given by intravenous infusion. Epidermal growth factor receptor (EGFR) is commonly overexpressed or constitutively activated in HNC, including OSCC, and is known to contribute to their uncontrolled proliferation, poor prognosis, and survival (Chung et al. 2006). Hence, blocking the EGFR pathway has been regarded as a promising molecular target for HNC (Boeckx et al. 2014). Unfortunately, only 10%–20% of patients with HNC tumors display a favorable response to cetuximab monotherapy, and even the combination of standard chemotherapies with cetuximab treatment prolongs overall survival by a few months because of resistance to EGFR pathway inhibition (Ratushny et al. 2009; Boeckx et al. 2014). Therefore, new therapeutic approaches, including rational combination strategies, are needed to increase the long-term survival of OSCC patients.
Recurrent Pregnancy Loss from Evidence-Based to Personalized Medicine
Howard J.A. Carp in Recurrent Pregnancy Loss, 2020
Personalized medicine has many major drawbacks. The development of new drugs and testing for genomic biomarkers is expensive. For example, cetuximab is used for treating late-stage colorectal cancer. However, it is only effective in patients in whom the the KRAS gene is not mutated [20]. KRAS mutational analysis is commercially available from a number of laboratories. Cetuximab is approved by the FDA in the United States after KRAS testing in order to identify those individuals who have a high chance of responding. However, the average extension of life is 5 months. Consequently, in 2006, the UK's National Institute for Health and Clinical Excellence did not approve this drug for use on the National Health Service (NHS), because at a cost of over £11,000 this was “not compatible with the best use of NHS resources.”
Antibody-Based Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Cetuximab (ErbituxTM) is a chimeric (mouse/human) IgG1 antibody that targets the extracellular domain of EGFR which is overexpressed in approximately 35% of tumor types. It comprises the Fv regions of an anti-EGFR mouse antibody with kappa light chain and human IgG1 heavy chain constant regions. Cetuximab was developed by Bristol-Myers Squibb/Eli Lilly/Merck, and first approved in 2004 for colorectal cancer. Subsequent approvals include use in advanced squamous cell carcinoma of the head and neck (2006), recurrent locoregional or metastatic squamous cell head and neck cancer (2011), and EGFR-expressing metastatic colorectal cancer (2012). Once bound to the receptor, cetuximab works by competitively inhibiting ligand binding, thereby preventing EGFR activation and subsequent cellular signaling. It also induces ADCC and leads to increased levels of the Bax protein, which can activate apoptosis.
Bioanalytical strategies in drug discovery and development
Published in Drug Metabolism Reviews, 2021
Aarzoo Thakur, Zhiyuan Tan, Tsubasa Kameyama, Eman El-Khateeb, Shakti Nagpal, Stephanie Malone, Rohitash Jamwal, Chukwunonso K. Nwabufo
Biologics are a vast class of drugs that include products, such as mAbs, vaccines, growth factors, enzymes, hormones, antibody fragments, antibody-drug conjugates (ADCs), protein diagnostics, etc. (Shi 2014). They are classified into four groups. Group I include protein therapeutics with enzymatic or regulatory activity, like insulin for the treatment of diabetes. Biologics with special targeting activity belong to Group II. Cetuximab, an epidermal growth factor inhibitor, used for the treatment of colorectal cancer and head and neck cancer, belongs to Group II. Group III and Group IV include protein vaccines (like HPV vaccine) and protein diagnostics (like Arcitumomab, Capromab pendetide, etc.), respectively (Leader et al. 2008). During the past few years, a lot of biologics have entered the market. Based on the latest evaluation, by 2022, biologics will overtake small molecules and will contribute to 52% of the top 100 product sales (Eval. Pharma 2017). The cutting-edge research that discovers new biologics offers more effective means to treat a variety of illnesses and conditions (U.S. FDA 2018). Through innovative breakthroughs, such as protein engineering, genomic medicines, etc., biologics have made more progress in healthcare development than small molecules (Makurvet 2021).
Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells
Published in Journal of Microencapsulation, 2018
Jitendrakumar Patel, Jitendra Amrutiya, Priyanka Bhatt, Ankit Javia, Mukul Jain, Ambikanandan Misra
Nowadays, nanotechnology based targeting approach (Javia and Thakkar 2017) is widely used to enhance therapeutic benefit, i.e. ligand conjugation like monoclonal antibody (mAb) on NPs surface in order to get drug localisation results in selective tumour targeting at the affected site (Bhatt et al.2016), while minimising off-target effects caused by non-selective drug accumulation to normal tissues (Yameen et al.2014). Monoclonal antibodies and small-molecule tyrosine kinase inhibitors are the two main types of therapy being used as a targeting approach in the treatment of NSCLC. mAb used to treat NSCLC includes bevacizumab and cetuximab (Adler and Dimitrov 2012). In which, cetuximab acts as a tyrosine kinase inhibitor and it binds to EGFR, which is a tyrosine kinase protein, on the surface of cancer cells and works to stop the cells from growing and dividing. These antibodies can selectively bind receptors on cancer cells or normal substrate having role in growth of cancer cells and attach to them. The result of antibody binding to such receptors or substrates can be seen in form of cancer cell killing, prevention of metastasis, or retardation of cancer cell growth (Green et al.2000, Wolpin 2015).
Advances in pharmacotherapy for head and neck cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Shikhar kumar, Vanita Noronha, Vijay Patil, Amit Joshi, Nandini Menon, Kumar Prabhash
In a phase I dose-finding study by Baselga et al. [7], it was demonstrated that cetuximab could be combined safely with cisplatin and that antibody doses in the range of 200 to 400 mg/m2 were associated with complete saturation of systemic clearance. The recommended phase II dose was 200 mg/m2. A subsequent phase Ib study by Shin et al. [8] showed that a loading dose of 400 mg/m2 with a maintenance dose of 250 mg/m2 achieved a high percentage of saturation of EGFR in the tumor tissue. A phase II study also demonstrated that cetuximab was effective, when given in combination with platinum-based chemotherapy, with an objective response rate (ORR) of 10% and disease control rate of 53%. The most common adverse effect of cetuximab was an acneiform skin rash [9].
Related Knowledge Centers
- Colorectal Cancer
- Epidermal Growth Factor Receptor
- Head & Neck Cancer
- KRAS
- Monoclonal Antibody
- Polymerase Chain Reaction
- Medication
- Head & Neck Cancer
- Panitumumab
- Companion Diagnostic
- Indication