Cancer suicide gene therapy: a patent review

ABSTRACT

Introduction: Cancer is considered the second leading cause of death worldwide despite the progress made in early detection and advances in classical therapies. Advancing in the fight against cancer requires the development of novel strategies, and the suicide gene transfer to tumor cells is providing new possibilities for cancer therapy.

Areas covered: In this manuscript, authors present an overview of suicide gene systems and the latest innovations done to enhance cancer suicide gene therapy strategies by i) improving vectors for targeted gene delivery using tissue specific promoter and receptors; ii) modification of the tropism; and iii) combining suicide genes and/or classical therapies for cancer. Finally, the authors highlight the main challenges to be addressed in the future.

Expert opinion: Even if many efforts are needed for suicide gene therapy to be a real alternative for cancer treatment, we believe that the significant progress made in the knowledge of cancer biology and characterization of cancer stem cells accompanied by the development of novel targeted vectors will enhance the effectiveness of this type of therapeutic strategy. Moreover, combined with current treatments, suicide gene therapy will improve the clinical outcome of patients with cancer in the future.

KEYWORDS:

• Cancer
• cancer stem cells
• suicide gene therapy
• targeted vectors
• tissue specific promoter

Article highlights

• Cancer still represents the major field of pre-clinical and clinical activities in gene therapy.

• The failure of the suicide gene therapy is due more to the lack of tumour specificity, than the safety of suicide genes. Thus, the development of targeted vectors is the key to successful gene delivery in cancerous cells.

• An improvement of vectors is paralleled by tremendous advancements in physical and chemical transfer technologies to aid efficient gene delivery.

• Recent pre-clinical and clinical studies in cancer models prove the enormous potential of suicide gene therapy when used in combination with classic therapeutic approaches such as chemotherapy and radiotherapy.

• Combination therapy can result in enhanced anti-cancer effects especially when treatments act in diverse pathways reaching all the cell types that make up the tumour including CSCs, making it a new promising strategy in cancer therapy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported in part by grants from the Ministerio de Economía y Competitividad (MINECO, FEDER funds, grant number MAT2015-62644-C2-2-R) and the Fundación Progreso y Salud (Consejería de Salud, Junta de Andalucía, Janssen Cilag S.A, project number PI-0533-2014).