Substance P and neurokinin-1 receptor were found in all thyroid cancer types with higher expression than normal tissue, suggesting NK-1R as a potential drug target.
All 4 cancer typespapillary, follicular, medullary, and anaplastic thyroid cancers all overexpress the NK-1 receptor drug target
What the researchers found
Both Substance P (SP) and the neurokinin-1 receptor (NK-1R) were expressed in all thyroid tissue, normal and cancerous. But the pattern differed significantly:
In healthy thyroid: SP was found in follicular cell nuclei and colloid. NK-1R was in follicular cell cytoplasm and stroma.
In thyroid cancer: SP expanded to follicular cell cytoplasm (not just nucleus), stroma, and colloid. NK-1R appeared in colloid (not present in normal tissue).
Using the Allred scoring system (a semi-quantitative measure of protein expression), both SP and NK-1R had higher total scores in cancer compared to normal thyroid. SP in nuclei, cytoplasm, and stroma was more intense/abundant in cancer. NK-1R in cytoplasm and colloid was higher in cancer.
Interestingly, SP in colloid was actually lower in cancer than in normal thyroid, and NK-1R in stroma was higher in normal tissue than cancer.
All four thyroid cancer types (papillary, follicular, medullary, anaplastic) and metastases showed the elevated pattern.
Why it matters
Thyroid cancer incidence has tripled over 30 years. While most cases have good prognosis with surgery, anaplastic thyroid cancer is nearly universally fatal. Finding that NK-1R is overexpressed in all thyroid cancer types, including anaplastic, opens a potential therapeutic target. NK-1R antagonists (originally developed for nausea and depression) have shown anticancer effects in preclinical studies.
The numbers in context
SP and NK-1R in all samples; higher Allred scores in cancer; all 4 cancer types + metastases affected; SP expanded to cytoplasm in cancer
How the study worked
Immunohistochemistry study of human thyroid tissue samples: papillary, follicular, medullary, and anaplastic thyroid cancer, metastases, and healthy thyroid. SP and NK-1R protein expression scored using the Allred Unit Scoring System (combines intensity and proportion).
Who was studied
Human thyroid cancer samples (papillary, follicular, medullary, anaplastic) and normal thyroid tissue
What this study cannot tell us
Immunohistochemistry shows presence but not function. Higher expression does not prove SP/NK-1R drives cancer growth. No functional studies (NK-1R antagonist testing on thyroid cancer cells). Sample sizes per cancer type not specified in the abstract. Semi-quantitative scoring is subjective. The study did not measure SP/NK-1R correlation with cancer aggressiveness or patient outcomes.
How to read the evidence
Preliminary evidence from immunohistochemistry. Expression is demonstrated but functional role and therapeutic potential are not tested.
When this study was published
Published in 2020. NK-1R targeting in cancer is being explored across multiple tumor types.
The bigger picture
Thyroid cancer incidence has tripled over 30 years. While most types are treatable, anaplastic thyroid cancer is nearly always fatal. NK-1R overexpression across all types, including anaplastic, suggests a common drug target for this diverse cancer family.
Questions still open
- Would NK-1R antagonists like aprepitant have anti-tumor effects in thyroid cancer?
- Does SP/NK-1R signaling drive thyroid cancer growth or is it a bystander?
- Could NK-1R expression serve as a diagnostic or prognostic marker?
Common questions
What is the NK-1 receptor and why target it in cancer?
Does this mean Substance P causes thyroid cancer?
Read the original research
The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.
European journal of histochemistry : EJH, 64(2)
Citation
Isorna, Inmaculada; Esteban, Francisco; Solanellas, Juan; Coveñas, Rafael; Muñoz, Miguel. (2020). The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.. European journal of histochemistry : EJH, 64(2). https://doi.org/10.4081/ejh.2020.3117