Are sigma modulators an effective opportunity for cancer treatment? A patent overview (1996-2016)

ABSTRACT

Introduction: Although several molecular targets against cancer have been identified, there is a continuous need for new therapeutic strategies. Sigma Receptors (SRs) overexpression has been recently associated with different cancer conditions. Therefore, novel anticancer agents targeting SRs may increase the specificity of therapies, overcoming some of the common drawbacks of conventional chemotherapy.

Areas covered: The present review focuses on patent documents disclosing SR modulators with possible application in cancer therapy and diagnosis. The analysis reviews patents of the last two decades (1996–2016); patents were grouped according to target subtypes (S1R, S2R, pan-SRs) and relevant Applicants. The literature was searched through Espacenet, ISI Web, PatentScope and PubMed databases.

Expert opinion: The number of patents related to SRs and cancer has increased in the last twenty years, confirming the importance of this receptor family as valuable target against neoplasias. Despite their short history in the cancer scenario, many SR modulators are at pre-clinical stage and one is undergoing a phase II clinical trial. SRs ligands may represent a powerful source of innovative antitumor therapeutics. Further investigation is needed for validating SR modulators as anti-cancer drugs. We strongly hope that this review could stimulate the interest of both Academia and pharmaceutical companies.

KEYWORDS:

• Cancer
• diagnostic and therapeutic tools
• drug conjugates
• sigma receptors (SRs)
• pan-SR ligands
• S1R and S2R modulators

Article highlights

• Conventional chemotherapy is becoming more and more effective. However, it brings important issues, such as poor specificity and side effects. The need for novel therapeutic targets is still unmet;

• In the last two decades, Sigma Receptors overexpression has been observed in several tumour types (e.g. pancreatic adenocarcinoma and breast cancer);

• SRs have been only recently associated to cancer conditions, although growing evidence supports their value as potential targets for anticancer drugs;

• Despite the numerous SR ligands designed, only [18F]-ISO-1 is undergoing a Phase II clinical trial for the diagnosis of primary breast cancer;

• Multiple strategies have been employed for developing new anticancer agents targeting SRs. S1R ligands re-evaluation and drug conjugates seem the most promising approaches in the patent literature.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank Dr. Francesca Negri (University of Pavia) for the support in patent literature search and analysis.

Declaration of interest

The authors have no 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

No funding to declare.