5 Potential Therapeutic Targets for Small Cell Lung Cancer

Researchers have identified 5 key genes that may serve as new treatment targets for small cell lung cancer (SCLC), according to research published in Frontiers in Immunology.1

The study found that 2 genes—PSAT1 and PSRC1—were upregulated in SCLC and linked to increased disease risk, while 3 others—COLEC12, PLLP, and HP—were downregulated and associated with immune response regulation. Notably, high expression of PSRC1 correlated with lower survival rates, making it a compelling target for further research.

According to the authors, this new research offers hope for more targeted treatment approaches by identifying genetic pathways that could be exploited for drug development.

1. PSAT1 and Cancer Cell Metabolism

PSAT1 plays a crucial role in the serine and glycine metabolic pathway, which fuels cancer cell growth. The study showed that PSAT1 is significantly upregulated in SCLC, linking it to aggressive tumor progression.

Researchers found that PSAT1 contributes to multiple pathways involved in cancer cell proliferation. With a lack of studies looking at PSAT1 in SCLC, the authors said their results “may reveal a new research direction for an in-depth exploration of the pathogenesis of SCLC.”

In the non–small cell lung cancer (NSCLC) space, prior research indicates PSAT1 overexpression enhances tumor survival and treatment resistance, making it a promising target for metabolic therapies.2 According to the researchers, by disrupting PSAT1-driven metabolic pathways, future treatments could slow SCLC progression and improve patient outcomes.1

2. PSRC1 and Poor SCLC Survival

Among the 5 genes, PSRC1 stood out due to its strong association with poor survival in patients with SCLC. The study found that patients with high PSRC1 expression had significantly lower survival rates than those with lower levels.

“Based on these findings, we speculate that its elevated expression may promote cell cycle progression, thereby accelerating the development of small cell lung cancer,” they wrote. “Moreover, the survival analysis has demonstrated that the elevated expression of PSRC1 correlates with a lower survival rate in SCLC, which aligns with the circumstances observed in non-small cell lung cancer. In view of these findings, we believe that PSRC1 may be a potential therapeutic target for SCLC.”

Importantly, the study lacks biological experiments to validate the bioinformatics findings. | Image credit: DragonImages – stock.adobe.com

Previous NSCLC studies have also suggested a possible connection between PSAT1 and PSRC1, where higher PSAT1 expression prevents the breakdown of the cell cycle protein D1 while increased PSRC1 expression stimulates its production.3

“Because of the limited research on these two genes in SCLC currently, it is still uncertain whether such a combined action exists in SCLC, yet our research may offer a new research direction,” the authors noted.1

3. COLEC12 and the Immune System

COLEC12 is a scavenger receptor involved in recognizing pathogens and initiating immune responses, making it a crucial component of host defense. While previous studies have linked elevated COLEC12 expression to tumor progression in gastric and colon cancers, the current study found that COLEC12 expression was downregulated in SCLC, suggesting a different role in this disease.

“Moreover, the enrichment analysis revealed that it is involved in biological functions and pathways such as endocytic vesicle, scavenger receptor activity, and phagosome,” the authors noted.

COLEC12 plays a role in macrophage activation and pathogen clearance, both of which are critical for immune surveillance. According to the authors, reduced COLEC12 levels may weaken immune surveillance, potentially allowing cancer cells to evade detection and promoting SCLC progression. They again noted the lack of research on the specific gene in SCLC.

4. HP and Oxidative Stress

The HP gene encodes a protein that binds free hemoglobin to prevent oxidative damage and inflammation. The study found that HP was downregulated in SCLC, which may contribute to increased oxidative stress, a factor known to promote cancer progression. Prior studies have linked high HP levels to disease severity in NSCLC, but in SCLC, reduced HP expression may impair the body's ability to counteract inflammation and oxidative damage.

“We presume that the decreased expression of HP in tumor tissues may inhibit this regulatory pathway, thereby weakening the antioxidant and anti-inflammatory effects and promoting the development of SCLC,” the authors wrote, again noting limited research.

5. PLLP: A Possible Connection to SCLC’s Neuroendocrine Features

PLLP is a membrane protein involved in myelin formation and neural signaling, with prior research linking PLLP with brain metastases in breast cancer and melanoma in mouse models. The current study found that PLLP was significantly downregulated in SCLC, pointing towards a possible connection between SCLC and neuroendocrine characteristics. An enrichment analysis also suggests the gene plays a role in biological functions related to compact myelin, the myelin sheath, and the structural components of myelin.

Again noting limited research and a need for more, the authors speculated that the reason why decreased expression of PLLP can promote the development of SCLC may be related to the neuroendocrine characteristics of the disease.

This study has several limitations, primarily the lack of biological experiments to validate the bioinformatics findings. Additionally, due to incomplete dataset information, key factors such as age, gender, and disease stage were not analyzed. Future research will focus on clinical studies and laboratory validation to strengthen these findings and explore their potential for therapeutic applications in SCLC.

References

1. Liao Z, Jia P, Li Y, Zheng Z, Zhang J. Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis. Front Immunol. 2025;15:1464259. doi:10.3389/fimmu.2024.1464259
2. Feng M, Cui H, Tu W, et al. An integrated pan-cancer analysis of PSAT1: a potential biomarker for survival and immunotherapy. Front Genet. 2022;13:975381. doi:10.3389/fgene.2022.975381
3. Yang Y, Wu J, Cai J, et al. PSAT1 regulates cyclin D1 degradation and sustains proliferation of non-small cell lung cancer cells. Int J Cancer. 2015;136(4):E39-E50. doi:10.1002/ijc.29150