Oncology

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Are We Ready To Tackle Small-Cell Lung Cancer?

by Federica Parisi PhD, October 27, 2015 at 09:57 AM | Tags

Small-cell lung carcinoma (SCLC) accounts for 20% of the total number of lung cancer cases worldwide. SCLC patients have limited treatment options, especially when they present with metastatic disease. During this year ASCO Meeting results from two trials were presented showing promising data on the application of immunotherapy with PD-1 agents to relapsed SCLC, bringing some hope for tackling the disease.

Lung cancer is the most common type of cancer worldwide, accounting for 13% of the total number of new diagnoses. For therapeutic purposes, lung cancer is classified according to the size and appearance of the malignant cells. Two broad classes are distinguished: non-small cell lung carcinoma (NSCLC), accounting for 80% of all lung cancer cases and small-cell lung carcinoma (SCLC), mostly arising in the respiratory airways (bronchi) and strongly related to smoking. Although less common than NSCLC, SCLC is characterized by rapid growth and early development of metastases. SCLC is highly responsive to both chemotherapy and radiotherapy, however it commonly relapses within months despite treatment.

Current SCLC therapy approaches have not resulted in major advances in the treatment of the disease in more than twenty years.

Historically, efforts at characterizing the molecular underpinnings of SCLC have lagged behind those of NSCLC. Many of the 'driver' mutations found in lung adenocarcinoma are only rarely found in SCLC. Moreover, newer agents, such as Avastin® (bevacizumab) and Alimta® (pemetrexed) are not approved for or exhibit diminished efficacy in SCLC. Thus, patients with metastatic SCLC have fewer treatment options than those with NSCLC. Despite these caveats, 'driver' mutations that may be linked to outcomes with targeted therapies in SCLC are emerging.

During this year ASCO meeting, two abstracts were presented at the Lung Cancer Oral Abstract Session reporting on the results of two large studies – the KEYNOTE-028 and the CHECKMATE-032 trials – on PD-1 therapies for the treatment of patients with SCLC.

Both studies present extremely encouraging results for heavily pretreated patients with SCLC, that for the first time show durable response. However, since the trials are currently ongoing they cannot be considered as definitive data and consistently more efforts will be made in the near future to optimize treatment strategies for this disease.

Crown Bioscience has a long standing track record of success in SCLC and immunotherapy preclinical research. Most oncology dugs fail during late stage clinical trials because of efficacy, rather than toxicity issues. This underlines a poor preclinical strategy and the lack of an associated clinical plan. At Crown Bioscience our mission is to help our clients' drug discovery program succeed.

Crown has developed the largest and most comprehensive commercially available collection of SCLC PDX models, encompassing models coming from many different lesions, allowing us to capture the diversity observed in the patient population. Our PDX collection (HuPrime® and PDXact™ JumpStart) has been trialed for in vivo response to standard of care agents (platinum/etoposide). Interestingly some of our models show an initial response that is followed by a rapid relapse, similarly to what has been observed in the clinic. Our PDX models are an extremely valuable toolset to run HuTrials™, mouse avatar clinical trials, in which to evaluate the efficacy of novel anticancer compounds and stratify your patient population by identifying responders versus non-responders.

Our immunotherapy resources include syngenic (bioluminescent and metastatic) models, GEMM, MuPrime™ (the murine version of HuPrime®), HuMice (humanized mice produced through inoculating human hematopoietic cells into immunocompromised mice), and MiXeno (creating transient human immunity by mixing human peripheral blood mononucleated cells with xenograft models). We also support preclinical drug development through the use of our in vivo grade human and mouse isotype control antibodies.

For enquires about how we can help you accelerate your drug discovery program contact us today at busdev@crowbio.com.

Disclosure Statement

Crown Bioscience provides preclinical models and services for translational oncology and is not qualified to provide medical advice. For more information on clinical trials recruitment and current treatment options please refer to your doctor or visit the National Cancer Institute (NIH) and the National Health Service (NHS) websites.

 


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