Actinic Keratosis Treatment: Molecular Biology and Skin Cancer

Sun's Shadow: How Molecular Biology is Changing Skin Cancer Treatment

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Samir D’Costa in Health & Wellness December 2025 • 5 min read.

"Unlocking New Pathways for Daylight Photodynamic Therapy in Field Cancerization"


Actinic keratoses (AKs), those rough, scaly patches that pop up on sun-exposed skin, are more than just a cosmetic nuisance. They're actually considered in-situ squamous cell carcinomas (SCC), meaning they have the potential to invade deeper tissues and even spread. It's like a ticking clock, but the problem is, we can't always predict which AKs will turn aggressive.

Traditional treatments often target individual lesions, but AKs tend to appear in clusters across larger areas of sun-damaged skin – a phenomenon known as field cancerization. This is where daylight photodynamic therapy (dPDT) comes in. It treats the entire affected area, but questions remain about tailoring treatments and predicting outcomes.

Now, researchers are diving deep into the molecular biology of AKs, hoping to uncover clues that will help us identify high-risk lesions and personalize treatment strategies. Think of it as reading the fine print of your skin cells to better understand their behavior.

Decoding the Molecular Landscape of Actinic Keratosis

Actinic Keratosis Treatment: Molecular Biology and Skin Cancer

Imagine being able to look at an AK lesion and know, with a high degree of certainty, whether it's likely to progress to invasive cancer. That's the promise of molecular profiling. By analyzing the genes expressed in AK cells, scientists hope to create a risk assessment tool that goes beyond what we can see with the naked eye or even under a microscope.

A recent review of existing research has identified a set of eight genes that show significant changes in expression during the transition from healthy skin to AK and SCC. These genes play roles in everything from cell adhesion and tissue remodeling to inflammation and immune response. Here's a closer look:

  • MMP1 (Matrix Metalloproteinase 1): This enzyme breaks down the extracellular matrix, the scaffolding that supports tissues. High MMP1 levels are linked to cancer progression and invasion.
  • SPRR1B (Small Proline Rich Protein 1B): Involved in forming the protective outer layer of skin cells. Its role in cutaneous SCC is still being explored, but it may promote growth in cancer stem-like cells.
  • KLK6 (Kallikrein Related Peptidase 6): This protease participates in inflammation and tissue remodeling. It's associated with cancer development and may facilitate the spread of mucosal squamous cell carcinoma.
  • CDH3 (P-cadherin): A cell adhesion molecule that helps cells stick together. High levels of CDH3 are linked to invasiveness in various cancers, including SCC.
  • PI3 (Peptidase Inhibitor 3 or Elafin): This protein inhibits elastase, an enzyme that can break down proteins. It may also play a role in cell differentiation and apoptosis (programmed cell death) in esophageal SCC.
  • SPP1 (Secreted Phosphoprotein 1 or Osteopontin): This protein is involved in bone remodeling and acts as a cytokine, a signaling molecule that stimulates the immune system. It can activate EMT in colorectal cancer and may predict the severity of oral SCC.
  • FN1 (Fibronectin 1): This glycoprotein is involved in wound healing and blood clotting. It can promote cell migration and spreading in SCC cell lines and may be linked to radiation resistance.
  • INHBA (Inhibin Beta, Subunit A): This protein has been linked to various cancers and may play a role in lymph node metastasis in head and neck SCC.
Interestingly, most of these genes show increased activity in AK and SCC, suggesting they contribute to cancer development. However, some genes, like FN1 and INHBA, are downregulated in AK but upregulated in SCC, highlighting the complex molecular changes that occur as AK progresses to invasive cancer.

The Future of AK Treatment: Personalized and Proactive

By studying the expression of these genes in different types of AK and SCC, researchers hope to gain a deeper understanding of how these lesions develop and progress. This knowledge could lead to more precise risk assessments and personalized treatment strategies. Imagine a future where your dermatologist can use a molecular test to determine your risk of developing invasive skin cancer and tailor your treatment accordingly. This is where molecular biology meets personalized medicine, paving the way for more effective and proactive skin cancer prevention.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.23736/s0392-0488.18.06015-7, Alternate LINK

Title: Daylight Photodynamic Therapy For Field Cancerization: Lessons From Molecular Biology

Subject: Dermatology

Journal: Giornale Italiano di Dermatologia e Venereologia

Publisher: Edizioni Minerva Medica

Authors: Max Rybarski, Lutz Schmitz, Ben Novak, Thomas Dirschka

Published: 2018-12-01

Everything You Need To Know

1

What exactly are actinic keratoses and why should I be concerned about them?

Actinic keratoses (AKs) are rough, scaly patches on sun-exposed skin that are considered in-situ squamous cell carcinomas (SCC). This means they have the potential to invade deeper tissues and spread, although it's difficult to predict which AKs will become aggressive. The risk lies in their potential to progress into invasive cancer if left untreated.

2

What is daylight photodynamic therapy, and why is it used to treat sun-damaged skin?

Daylight photodynamic therapy (dPDT) is a treatment that addresses the entire area affected by field cancerization, where AKs appear in clusters on sun-damaged skin. It's important because traditional treatments often target individual lesions, missing the broader scope of the problem. However, optimizing dPDT requires a better understanding of how to tailor treatments and predict outcomes.

3

What is molecular profiling and how can it help with actinic keratosis?

Molecular profiling is analyzing the genes expressed in AK cells to assess the risk of progression to invasive cancer. This is significant because it offers a deeper understanding beyond what can be observed with the naked eye or under a microscope. It allows for a more accurate prediction of which AK lesions are likely to become aggressive.

4

What are some of the key genes involved in the development of actinic keratosis and squamous cell carcinoma, and what do they do?

Several genes, including MMP1, SPRR1B, KLK6, CDH3, PI3, SPP1, FN1, and INHBA, show altered expression during the transition from healthy skin to AK and SCC. Most of these genes show increased activity in AK and SCC, suggesting they contribute to cancer development. However, some, like FN1 and INHBA, behave differently in AK versus SCC, highlighting the complexity of molecular changes during cancer progression. Studying these genes provides insights into cancer development and potential therapeutic targets.

5

How can molecular biology lead to more personalized treatments for actinic keratosis?

Personalized medicine in AK treatment involves using molecular tests to determine an individual's risk of developing invasive skin cancer and tailoring treatment accordingly. This approach allows for more effective and proactive prevention strategies, moving away from a one-size-fits-all approach. It could involve more frequent monitoring, targeted therapies, or lifestyle changes based on the individual's molecular profile.

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