MYC, MYCL, and MYCN as therapeutic targets in lung cancer

ABSTRACT

Introduction: Lung cancer is the leading cause of cancer-related mortality globally. Despite recent advances with personalized therapies and immunotherapy, the prognosis remains dire and recurrence is frequent. Myc is an oncogene deregulated in human cancers, including lung cancer, where it supports tumorigenic processes and progression. Elevated Myc levels have also been associated with resistance to therapy.

Areas covered: This article summarizes the genomic and transcriptomic studies that compile evidence for (i) MYC, MYCN, and MYCL amplification and overexpression in lung cancer patients, and (ii) their prognostic significance. We collected the most recent literature regarding the development of Myc inhibitors where the emphasis is on those inhibitors tested in lung cancer experimental models and their potential for future clinical application.

Expert opinion: The targeting of Myc in lung cancer is potentially an unprecedented opportunity for inhibiting a key player in tumor progression and maintenance and therapeutic resistance. Myc inhibitory strategies are on the path to their clinical application but further work is necessary for the assessment of their use in combination with standard treatment approaches. Given the role of Myc in immune suppression, a significant opportunity may exist in the combination of Myc inhibitors with immunotherapies.

KEYWORDS:

• Lung cancer
• immuno-oncology
• Myc
• Myc inhibition
• MYCL
• MYCN
• NSCLC
• Omomyc
• SCLC

Article Highlights

• The Myc family is aberrantly expressed in lung cancer

• Myc has a profound effect on lung cancer etiology and progression

• Myc has long been deemed an ‘undruggable’ protein thus precluding its consideration as potential actionable target

• Myc overexpression is often associated to resistance to therapy

• Myc’s role in the modulation of the tumor microenvironment represents an important vulnerability of lung cancer

• Novel Myc inhibitory strategies could offer novel therapeutic options for lung cancer patients

• Myc inhibition in the clinic could synergize with standard of care and current immune oncology therapies.

This box summarizes key points contained in the article.

Declaration of interest

L Soucek is a Founder, Board Member and shareholder of Peptomyc S.L., Barcelona, Spain.

ME Beaulieu is Founder, Board Member, shareholder and employee of Peptomyc S.L, Barcelona, Spain.

D Massó-Vallés is an employee of Peptomyc S.L., Barcelona, Spain.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The authors have received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC-2013-CoG grant no. 617473), The Ministerio de Ciencia e Innovación (Grant No. PTQ-17-09299) and the Agència de Gestió d'Ajuts Universitaris i de Recerca (Grant No. 2017 SGR 537).