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Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
[Gene therapy and molecular therapeutic for head and neck cancer]
1Dept. of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kobe University, Japan.
Abstract:
Despite recent progress in radiotherapy, chemotherapy and surgical techniques, the survival of patients with head and neck squamous cell carcinomas has not improved significantly over the past three decades. To conquer these malignant tumors, various new therapies have been under development, including gene therapies. In this paper, we have reviewed recent advances in gene therapies and molecular target therapy for head and neck cancers, with a special focus on the replication-selective adenovirus vector. At present, replication-defective adenovirus-based vectors have been widely used as convenient and safe vectors for transferring therapeutic genes into target cancer cells. However, these vectors have limited the efficacy of treatment by restricting the number of tumor cells to which the therapeutic gene can be delivered. Replication-selective adenoviral vectors (RSAV) are adenoviruses designed to have a limited ability to replicate themselves in the targeted tumor cells but not in other normal tissues. Tumor cell killing is achieved not by the genes delivered by the vectors but by the oncolysis induced by the replicated viruses by their original nature as adenovirus. Amplified viral vectors also spread to the adjacent tumor cells and kill these cells in the same manner. Recently, increased evidences of antitumor activity of RSAVs have been demonstrated preclinically, and several clinical trials have demonstrated the safety and clinical activity of replication-selective viruses.
Insights
Replication-selective adenoviral vectors (RSAV) show promise for head and neck cancers. These viruses selectively kill tumor cells via oncolysis, offering a new therapeutic avenue beyond traditional treatments.
Area of Science:
- Oncolytic virotherapy
- Gene therapy for cancer
- Head and neck cancer research
Context:
- Head and neck squamous cell carcinomas (HNSCC) show poor survival rates despite advances in conventional therapies.
- Existing gene therapy vectors, like replication-defective adenoviruses, have limitations in tumor cell transduction efficiency.
- New therapeutic strategies are crucial for improving HNSCC patient outcomes.
Purpose:
- To review recent advancements in gene and molecular target therapies for head and neck cancers.
- To highlight the potential of replication-selective adenoviral vectors (RSAV) in HNSCC treatment.
- To discuss the mechanism of action and preclinical/clinical evidence for RSAVs.
Summary:
- Replication-selective adenoviral vectors (RSAV) are engineered adenoviruses that replicate within tumor cells but not normal tissues.
- RSAVs induce tumor cell death through oncolysis, with amplified viruses spreading to adjacent cancer cells.
- Preclinical studies and clinical trials indicate promising antitumor activity, safety, and efficacy of RSAVs.
Impact:
- RSAVs offer a novel oncolytic approach for HNSCC, potentially overcoming limitations of current gene therapies.
- The selective replication and tumor-cell-killing mechanism of RSAVs presents a promising strategy for cancer treatment.
- Further clinical development of RSAVs could lead to improved therapeutic options for patients with head and neck cancers.
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