In the field of cancer treatment, epidermal growth factor receptor inhibitors (EGFRi) are a double-edged sword - they can accurately block the growth signals of tumor cells, significantly prolonging the survival of patients with lung cancer, colorectal cancer, and other diseases. However, up to 60% -90% of drug users may experience rash side effects, and in severe cases, they need to be reduced or even stopped, greatly affecting the treatment effect and patient's quality of life.

To address this clinical pain point, it is necessary to first understand the mechanism of EGFRi induced rash, and the EGFRi induced SD rat rash model is the core tool for researchers to explore this issue.

The scientific logic of model selection

1、 Why study 'EGFRi related rash'?

The epidermal growth factor receptor (EGFR) is not only present in tumor cells, but also widely distributed in normal skin epidermal cells and hair follicle epithelial cells, responsible for regulating physiological processes such as skin barrier repair and hair follicle growth. When EGFRi inhibits tumor cell EGFR, it can also "accidentally damage" EGFR in the skin, leading to:

• Damaged skin barrier function: Slow proliferation and abnormal differentiation of epidermal cells make the skin fragile and easily irritated;

• Inflammatory response activation: Immune cells aggregate and release inflammatory factors (such as IL-6 and TNF - α), causing redness, swelling, and itching;

• Abnormal hair follicles: Dyskeratosis of hair follicles, resulting in acne like rash.

In clinical practice, EGFRi related rashes often appear 1-2 weeks after medication and are more common on the face, chest, and back, presenting as erythema, papules, and pustules. In severe cases, severe itching, peeling, and even secondary infection may occur. However, due to the large individual differences, it is difficult for clinical studies to accurately control variables. Therefore, animal models are needed to explore the mechanism of rash occurrence and treatment plans under standardized conditions - this is the core value of the SD rat rash model.

2、 Why choose SD rats?

To test the effectiveness of tacrolimus ointment, the first step is to have a "reliable rash model". Three key reasons for selecting SD rats:

• Skin structure similar to that of humans: The epidermal thickness and hair follicle density of SD rats are highly similar to human skin, and the pathological process of rash occurrence (such as epidermal thickening and inflammatory cell infiltration) is highly consistent with human EGFRi related rashes;

• Strong model stability: The genetic background, weight, and health status of SD rats in the same batch are similar. When EGFRi is used to induce rash, the time and severity of appearance are more uniform, and the experimental data is more reliable;

• High operational convenience: SD rats have a moderate body size (adult weight 200-300g), which is convenient for applying ointment, observing changes in rash, and collecting skin tissue for pathological analysis in the future.

3、 How to make SD rats "suffer" from rash?

To successfully build a model, it is necessary to strictly control the three core aspects of "drug selection, dosing regimen, and observation indicators". The commonly used modeling process in scientific research is as follows, which can be used as a reference for researchers in related fields:

1. Experimental preparation: Rats and drug selection

• Experimental animals: Female SD rats aged 6-8 weeks are usually selected (female rats have more sensitive skin to EGFRi and a higher incidence of rash), with a body weight of 200-220g. The feeding environment is controlled at a temperature of 22-25 ℃ and humidity of 50% -60%. The experiment begins after one week of adaptive feeding.

• EGFRi drugs: commonly used clinically approved drugs, such as Erlotinib, Gefitinib, or Cetuximab. Among them, erlotinib is the most commonly used modeling drug due to its good water solubility and high rat rash induction rate (up to 80% or more).

2. Medication regimen: precise control of dosage and cycle

The route and dosage of administration are the key to the success of the model. There are currently two mainstream solutions:

• Intraperitoneal injection administration: Erlotinib is prepared into a drug solution with a concentration of 10-20mg/kg using physiological saline (or a small amount of DMSO as a solubilizer), and administered intraperitoneally once a day for 14-21 days. This method of drug absorption is stable and can quickly reach blood drug concentration, usually resulting in obvious rash 7-10 days after administration.

• Gavage administration: If simulating a clinical oral administration scenario, erlotinib can be mixed into rat feed or made into a suspension for gavage at a slightly higher dose (20-30mg/kg). The administration period is 21-28 days, and the rash appears slightly later than intraperitoneal injection, but it is closer to the clinical medication method.

KCI BioTech Skin Disease Pharmacology and Pharmacology Evaluation Platform

Case study of EGFRi induced rash model in SD rats

01 Erlotinib induced rat rash model and its efficacy

data display

• Skin rash rating

• a-Histopathological examination of epidermal and dermal thickness, b-Histopathological examination of inflammation within the epidermis and dermis c-IHC-CD68、d-IHC-ki67

• a-qPCR-IL-1β、b-qPCR-TNF-α

02 Afatinib induced rat rash model

data display

• Skin rash rating

• a-Histopathological examination of epidermal and dermal thickness, b-Histopathological examination of inflammation within the epidermis and dermis c-IHC-CD68、d-IHC-ki67

• qPCR