Can Targeting This 'Off' Switch Slow Lung Cancer?
"New Research Shows How Blocking PIGF May Disrupt Cancer Cell Growth"
Lung cancer remains one of the most formidable health challenges worldwide. While medical advancements continue, the complex nature of cancer cell behavior often requires multifaceted strategies. Recent studies are shedding light on how certain growth factors influence the spread of lung cancer, opening new avenues for potential treatments.
Among these growth factors, vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) have garnered attention. VEGF is well-known for its role in promoting blood vessel formation within tumors, facilitating their growth and spread. However, the specific role of PIGF in lung cancer metastasis—the process by which cancer cells spread to other parts of the body—has been less understood. But recent research suggests that PIGF plays a crucial role.
A new study published in Molecular Cell Biochemistry uncovers how PIGF signaling regulates the isoform splicing of vascular endothelial growth factor A, impacting lung cancer cell metastasis. The findings suggest that targeting PIGF could disrupt cancer cell growth and spread, offering a potential new therapeutic approach.
The Current U.S. Burden
The CDC reports that 228,058 new lung cancers were reported in the United States in 2023, while 128,663 people died from lung cancer in 2024. Its Lung Cancer Stat Bite also covers new cases, deaths, survival, and the percentage of people diagnosed at different stages. The CDC and National Cancer Institute provide detailed statistics by factors including sex, race, calendar year, age, stage, and histology. Lung metastasis is usually associated with poor outcomes in cancer patients.
Why Advanced Disease Is Difficult
Lung cancer can spread through lymphatic routes or blood vessels, with blood-borne spread potentially establishing distant metastases early. Common metastatic sites include the brain, bones, and adrenal glands, while other organs are usually involved later. Advanced lung cancer is more complex than earlier-stage disease and often requires a broader treatment approach. Mayo Clinic Press notes that treatment recommendations depend in part on whether the cancer is small-cell lung cancer or another type.
Tracing Metastatic Evolution
Metastasis is the process by which cancer cells spread from their original site to a secondary location, and the Nature source identifies it as the leading cause of cancer-related mortality. A 2021 study analyzed whole-exome sequencing from 40 primary tumors and 61 metastases from 47 patients with lung cancer. Researchers examined genomic divergence, metastatic drivers, the timing of dissemination, and evolutionary origins. However, reviews report that the evolutionary trajectories of lung cancer metastasis remain poorly understood, while the genomic and host factors driving progression of pre-invasive non-small cell lung cancer lesions are also incompletely understood.
How PIGF Fuels Lung Cancer Spread: The Key Findings
The research team compared tissue samples from patients with non-small cell lung cancer (NSCLC) to healthy lung tissue. They discovered significantly higher levels of PIGF in NSCLC samples. What’s more, patients with distal metastases (cancer that has spread to distant sites) had even higher PIGF levels, suggesting a link between PIGF and cancer progression.
- Higher PIGF in Cancerous Tissues: NSCLC specimens showed significantly elevated PIGF levels compared to adjacent normal lung tissue.
- Metastasis Link: Higher PIGF levels were detected in NSCLC specimens from patients with distal metastases, indicating a potential role in cancer spread.
- Poor Survival Association: High PIGF levels appeared to be associated with reduced overall survival in NSCLC patients.
Pathways Under Investigation
Research in human non-small-cell lung cancer H460 cells found that exposure to NiCl2 induced VEGF expression. Another study describes VEGF165 and VEGF165b as isoforms with the same length but opposite functions in cancer. Research on a novel short isoform of securin reported activation of cyclin D3 and the angiogenesis factors VEGFA and FGF2 in HEK293 cells, without affecting MYC transcription-factor expression. A recent review advocates patient stratification and combination therapies as a roadmap for future metastatic lung cancer research.
Progress Requires More Than Drugs
Despite new paradigm-shifting treatments, lung cancer remains a deadly disease. The reported challenge is broader than developing drugs alone, because improving outcomes requires addressing additional barriers. The Lung Ambition Alliance was launched in July as part of efforts to tackle those challenges. These points caution against assuming that a promising treatment mechanism by itself will solve lung cancer mortality.
Primary Tumor or Metastasis?
When multiple lung tumors appear at the same time, clinicians must distinguish separate primary lung adenocarcinomas from intrapulmonary metastasis if metastases from other organs can be excluded. The distinction is critical for cancer staging. If the tumors are synchronous multiple primaries, staging is determined by the tumor with the highest T factor. This comparison illustrates why similar-looking lesions can lead to different staging interpretations.
The Future of Lung Cancer Treatment: Targeting PIGF
These findings suggest that PIGF is more than just a bystander in lung cancer; it actively promotes cancer cell spread. Targeting PIGF, or the SRp40 pathway it influences, could offer a new strategy to slow or prevent lung cancer metastasis. While more research is needed to develop effective PIGF-blocking therapies, this study provides a promising step forward in the fight against lung cancer.
Consensus for Complex Decisions
The Society of Thoracic Surgeons expert consensus addresses the complex decision-making involved in managing locally advanced lung cancer. The expert panel agreed on several key recommendations based on updated evidence and literature. The document is intended to guide thoracic surgeons and other medical professionals. Its focus is management of locally advanced disease rather than a single experimental target.
Research Beyond the Switch
The American Association for Cancer Research Lung Cancer Task Force reports that targeted therapies, immunotherapy, and early detection have revolutionized treatment and extended survival. Despite those advances, lung cancer remains highly fatal. Its roadmap identifies knowledge gaps and proposes critical areas for future research. The agenda aligns with the mission of the AACR Lung Cancer Task Force.
From Symptoms to Real-World Evidence
Lung adenocarcinoma can metastasize to the liver, adrenal glands, brain, and bone, while soft-tissue metastases are rare and occur predominantly in men. A reported case involved a 65-year-old male ex-smoker with a nocturnal cough who was diagnosed with metastatic non-small-cell lung cancer and treated with cisplatin and gemcitabine. Real-world case reports also describe unexplained symptoms such as persistent cough, shortness of breath, or chest pain being initially dismissed, with delays in diagnosis common in non-small-cell lung cancer. Real-world data studies can help address evidence gaps because they collect information at the point of care rather than through randomized clinical trials.