Small Cell Lung Cancer (SCLC) is a neuroendocrine tumor that is characterized by rapid growth, early metastasis, and a strong association with cigarette smoking. Protheragen is committed to offering a comprehensive suite of services that are dedicated to advancing both diagnostics and therapeutics for SCLC.
Overview of Small Cell Lung Cancer (SCLC)
Small Cell Lung Cancer (SCLC) is a highly aggressive neuroendocrine tumor, accounting for around 13-15% of all lung cancers. It is distinguished by its rapid doubling time, high growth fraction, and early metastasis. SCLC has a strong association with smoking and is notorious for its poor prognosis. Without therapy, the median survival is only 2-4 months, and less than 5% of patients survive for 5 years. Despite recent therapeutic advances, SCLC remains an extremely challenging disease to treat effectively.
Fig.1 Representative therapeutic targets of interest in SCLC. (Rudin C. M.,
et al., 2021)
Pathogenesis of Small Cell Lung Cancer (SCLC)
The development of SCLC is complex, driven by genetic mutations and molecular changes that cause uncontrolled cell growth and early metastasis. A key step in SCLC development is the inactivation of the TP53 and RB1 genes. These genetic changes lead to the loss of tumor-suppressing functions, enabling cells to keep growing, avoid aging, and escape death. As more cancer-causing mutations build up, precancerous cells turn into malignant SCLC cells. Comprehensive genomic analyses have also found additional mutations in genes like RBL1, RBL2, CDKN2A, EP300, CREBBP, and others, which play a role in the development and progression of SCLC.
Diagnostics Development for Small Cell Lung Cancer (SCLC)
Liquid Biopsies
Development of assays to detect circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) in blood. These can provide real-time information on tumor burden, genomic alterations, and resistance mechanisms without the need for invasive tissue biopsies.
Proteomic Biomarkers
Discovery and validation of protein biomarkers in biological fluids (e.g., serum, plasma) or tissue samples that correlate with SCLC presence, stage, or response to therapy. Mass spectrometry-based approaches are often employed.
Transcriptomic Profiling
Identifying specific gene expression signatures that distinguish SCLC subtypes, predict sensitivity to certain drugs, or indicate disease progression. This involves techniques like RNA sequencing.
Imaging Biomarkers
While primarily clinical, preclinical work can involve developing novel imaging agents or techniques for PET or MRI that can specifically visualize SCLC tumors or their metabolic characteristics.
Therapeutics Development for Small Cell Lung Cancer (SCLC)
- Targeted Therapies: These drugs are designed to interfere with specific molecular pathways involved in cancer cell growth, progression, and spread. Given the frequent TP53 and RB1 aberrations, therapies that leverage synthetic lethality or target downstream effectors are being explored. For instance, Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, have shown promise, particularly in combination with immunotherapy, by exploiting deficiencies in DNA repair pathways often found in SCLC.
- Immunotherapy: Harnessing the body's own immune system to fight cancer has emerged as a significant therapeutic strategy. Immune checkpoint inhibitors, such as durvalumab and atezolizumab, which block negative regulators of T-cell activity, have demonstrated efficacy in improving outcomes for SCLC patients, especially in combination with chemotherapy.
Table 1. Ongoing clinical trials in patients with deficient p53 and retinoblastoma (Rb) SCLC. (Papavassiliou K. A., et al., 2024)
| Agent |
NCT ID Number |
Phase |
Therapeutics |
| AURK inhibitors |
NCT05271292 |
Ib/II |
Chiauranib |
| NCT05505825 |
Ib/II |
AK104 + Chiauranib |
| NCT03216343 |
I |
Chiauranib |
| NCT04830813 |
III |
Chiauranib Capsule |
| NCT06095505 |
II |
Alisertib |
| CDK7 inhibitors |
NCT04247126 |
I |
SY 5609 + gemcitabine |
| PARP inhibitors |
NCT05002868 |
I |
RP12146 |
| NCT03227016 |
I |
Veliparib + Topotecan |
| NCT04826341 |
I/II |
Sacituzumab Govitecan + Berzosertib |
| NCT03830918 |
I/II |
Niraparib + Temozolomide + Atezolizumab |
| NCT05975944 |
I/II |
Olaparib + Selinexor |
| NCT02769962 |
I/II |
EP0057 + Olaparib |
| NCT04434482 |
I/II |
IMP4297 + Temozolomide |
| NCT04538378 |
II |
Olaparib + Durvalumab |
| NCT05411679 |
II |
EP0057 + Olaparib |
| NCT05718323 |
II |
Niraparib + Anti-PD-L1 therapy |
| NCT04334941 |
II |
Talazoparib + Atezolizumab |
| NCT04939662 |
II |
Olaparib + Bevacizumab |
| ATR inhibitors |
NCT04491942 |
I |
Elimusertib + chemotherapy (cisplatin, or cisplatin and gemcitabine) |
| NCT02595931 |
I |
Berzosertib + Irinotecan hydrochloride |
| NCT04802174 |
I/II |
Berzosertib + Lurbinectedin |
| NCT04826341 |
I/II |
Berzosertib + Sacituzumab govitecan |
| NCT02487095 |
I/II |
Berzosertib + Topotecan |
| NCT03896503 |
II |
Berzosertib + Topotecan |
| ATM inhibitors |
NCT04939662 |
II |
Olaparib + Bevacizumab |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides comprehensive preclinical therapeutics development services for SCLC, utilizing cutting-edge technologies and a deep understanding of the disease's pathophysiology. Our services cover the entire spectrum from early-stage target discovery and validation to biomarker identification and preclinical drug development.
Disease Models
- SCLC Organoids with Fibroblasts
- Microbead-Based Tumor Organoids
- Trp53 and Rb Gene Knockout Models
- Patient-Derived Tumor Xenografts (PDTXs)
Protheragen provides a wide array of preclinical research services specifically tailored for SCLC. Our capabilities include establishing and characterizing patient-derived xenograft (PDX) models and cell line-derived xenograft (CDX) models that accurately recapitulate the heterogeneous nature of SCLC. We offer expertise in in vitro assays for drug sensitivity and resistance, including 2D and 3D cell culture models, high-throughput screening, and functional genomics. If you are interested in our services, please feel free to contact us.
References
- Rudin, Charles M., et al. "Small-cell lung cancer." Nature Reviews Disease Primers 7.1 (2021): 3.
- Papavassiliou, Kostas A., et al. "P53 and Rb aberrations in small cell lung cancer (SCLC): from molecular mechanisms to therapeutic modulation." International Journal of Molecular Sciences 25.5 (2024): 2479.
- Das, Millie, et al. "Advances in treatment of recurrent small cell lung cancer (SCLC): insights for optimizing patient outcomes from an expert roundtable discussion." Advances in Therapy (2021): 1-21.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
