Techniques For Targeted Molecular Therapy in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. The following is an overview of the techniques used for targeted molecular therapy in head and neck squamous cell carcinoma.

Targeted Molecular Therapy in Head and Neck Squamous Cell Carcinoma


It is estimated that in 2020, there will be about 833,000 new patients with head and neck cancer (primarily squamous cell carcinoma [SCC]) worldwide. [1] Early stage head and neck squamous cell carcinoma (HNSCC) is treated relatively well with single-modality therapy (either surgery or radiation alone). However, nearly 66% of patients present with advanced disease (stage III and IV), and fewer than 30% of these patients are cured.

The management of advanced HNSCC consists of multiple-modality therapy with surgery, radiation, and chemotherapy. Despite significant improvements in these modalities, long-term survival rates in patients with advanced-stage HNSCC have not increased significantly in the past 30 years.

Selective versus nonselective therapies

The current conventional modalities (surgery, radiation, chemotherapy) are nonselective and can cause damage to normal tissue. In particular, chemoradiotherapy is associated with systemic toxicities that often reduce compliance and prevent timely completion of therapy. [2] In an attempt to improve outcomes in HNSCC, most research in the field is now focusing on the molecular biology of HNSCC in an attempt to target select pathways involved in carcinogenesis. [3, 4]

With the increased understanding of molecular mechanisms and basic pathways in the pathogenesis of squamous cell cancer of the head and neck, these pathways may be modified, and rational approaches in cancer therapy at the molecular level may be created. Some of the new approaches depend on tumor biology and aim specifically to inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature (leaving normal cells unaffected) or focusing on specific protein or signal transduction pathways. [5]

The goal of specific molecular targets in cancer therapy is to create a “magic bullet” that selectively kills cancer cells. As our understanding of the molecular biology of HNSCC continues to develop, we can target the specific components of cancer cells that are not found in normal cells. Ideal targets should be both specific to cancer cells and commonly found in cancer cells.

Targeted molecular therapy, like therapy with monoclonal antibodies, gene therapy, and other therapies, has limited or nonexistent side effects on normal cells of the body, unlike present modalities such as surgery, chemotherapy, and radiotherapy. Targeted molecular therapy can also act as a complement to other existing cancer therapies. Scientists are constantly working on new cures and types of therapy. For example, in our department, there is a team dedicated to lentivirus packaging and production. Gene therapy is a big focus in the medical field at the minute.


The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. This family, which includes epidermal growth factor receptor (EGFR), plays a pivotal role in normal cell growth, lineage determination, repair, and functional differentiation. [6, 7, 8] Overexpression of EGFR is recognized in more than 80% of squamous cell cancers, and this overexpression is associated with a poor prognosis.

Targeted molecular therapy against EGFR has shown promise as an adjuvant therapy in preliminary studies in several solid tumors, including head and neck cancer. Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). [9]

Techniques for Targeted Molecular Therapy

Various techniques have been developed for targeting cancer cells: gene therapy, monoclonal antibodies (MAbs), antibody toxin conjugates, small-molecule inhibitors, antisense molecules, and tumor vaccines.

The goal of gene therapy is to introduce new genetic material into cancer cells that selectively kills them without causing toxicity to the surrounding cells. This task can be accomplished by replacing tumor suppressor genes that have been lost or mutated, selectively inserting genes that produce cytotoxic substances, or modifying the immune system to destroy the tumor cells. The major barrier in successful gene therapy is producing a vector that selectively infects all tumor cells within a tumor.

MAbs and antibody toxin conjugates can be targeted to specific receptors or proteins found on cancer cells. MAbs can block receptors and prevent potential growth signals. Antibodies can also be conjugated to toxins and specifically kill the tumor cells they bind.

Antisense molecules are a small, complementary, single-stranded type of DNA that binds targeted messenger RNA (mRNA) within the cell and prevents specific protein translation. Antisense molecules can be targeted toward specific proteins that are crucial in tumorigenesis.

Small-molecule inhibitors can bind and inhibit specific receptors or enzymes in cancer cells. These small-molecule inhibitors can be targeted toward crucial steps in tumorigenesis.

Tumor vaccines act to stimulate the patient’s immune system to attack cancer cells. These tumor vaccines can be developed from a patient’s tumor cells. In this process, mRNA is isolated from a tumor biopsy sample, amplified, and incorporated into human antigen-presenting cells (APCs). The APCs are then intravenously given to the patient to stimulate the patient’s immune system to activate antitumor T cells.

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