Pre-clinical models of small cell lung cancer and the validation of therapeutic targets

ABSTRACT

Introduction: Small-cell lung cancer (SCLC) is an aggressive form of lung cancer that has a dismal prognosis. One of the factors hindering therapeutic developments for SCLC is that most SCLC is not surgically resected resulting in a paucity of material for analysis. To address this, significant efforts have been made by investigators to develop pre-clinical models of SCLC allowing for downstream target identification in this difficult to treat cancer.

Areas covered: In this review, we describe the current pre-clinical models that have been developed to interrogate SCLC, and outline the benefits and limitations associated with each. Using examples we show how each has been used to (i) improve our knowledge of this intractable cancer, and (ii) identify and validate potential therapeutic targets that (iii) are currently under development and testing within the clinic.

Expert opinion: The large numbers of preclinical models that have been developed have dramatically improved the ways in which we can examine SCLC and test therapeutic targets/interventions. The newer models are rapidly providing novel avenues for the design and testing of new therapeutics. Despite this many of these models have inherent flaws that limit the possibility of their use for individualized therapy decision-making for SCLC.

KEYWORDS:

• Small-cell lung cancer (SCLC)
• pre-clinical models
• heterogeneity
• drug resistance
• liquid biopsy

Article Highlights

• Small-cell Lung Cancer (SCLC) is an aggressive tumor with poor prognosis, characterized by the development of rapid resistance to chemotherapy.

• As surgical intervention is rare for SCLC, hypothesis testing has been hampered by a lack of available material.

• The development of pre-clinical models has allowed the identification and pre-clinical testing of novel new agents and therapeutic targets.

• Limitations exist for many of these models which preclude testing patients for individualized therapy although advances in this area suggest that this barrier may be overcome.

• Blood-based pre-clinical models may hold the key to this strategy allowing for ex vivo expansion of patients' tumor cells allowing for testing of samples for personalized therapy.

This box summarizes key points contained in the article.

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.

Reviewer Disclosures

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

Additional information

Funding

This paper was not funded.