Related Experiment Video
Updated: Apr 15, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Orally active αvβ3 integrin inhibitor MK-0429 reduces melanoma metastasis
Maureen Pickarski1, Alexa Gleason2, Bohumil Bednar2
1Bone Biology, Merck Research Laboratories, West Point, PA 19486, USA.
Abstract:
Melanoma remains one of the most aggressive types of cancer with a historically low survival rate. The αvβ3 integrin is involved in the progression of malignant melanoma. In the present study, the efficacy of MK-0429, a selective inhibitor of the αvβ3 integrin, was evaluated for its potential in the prevention of melanoma metastasis. Female B6D2F1 mice injected via the tail vein with murine B16F10 melanoma developed lung metastases within ~10 days. In the first experiment, the prevention of lung metastasis was assessed in the model treated with either vehicle, MK-0429 at 100 and 300 mg/kg orally twice daily or cyclophosphamide at 300 mg/kg, i.p. once daily. Study endpoints included determination of the study time period to achieve metastasis in lungs in this model, evaluation of the health effects on the study animals, the total number of lung colonies identified and lung tumor area. Unlike cyclophosphamide, the MK-0429 treatment did not lead to a significant weight reduction in mice. MK-0429 at 100 and 300 mg/kg reduced the number of metastatic tumor colonies by 64 and 57%, respectively, and the high dose also reduced the tumor area by 60% as compared to the vehicle. The second experiment employed B16F10 luciferase-expressing cells to examine the de novo progression of melanoma metastasis over 15 days with bioluminescent imaging of mice treated with MK-0429 at 300 mg/kg as compared to the vehicle. Tumor burden progressively advanced in the lungs of the B16F10-treated animals. However, MK-0429 reduced the progression of ventral and dorsal lung metastases by 22 and 38%, respectively, as compared to the vehicle, by study completion. Quantification of ex vivo tumor burden showed a 30-40% reduction in lung colonies by MK-0429. The two studies collectively demonstrated that MK-0429 was safe and efficacious in significantly decreasing melanoma metastasis in the lungs. The results emphasized the potential of MK-0429 as a novel, therapeutic agent for the prevention of metastatic melanoma.
Insights
MK-0429, an αvβ3 integrin inhibitor, effectively reduced melanoma lung metastasis in mice without causing weight loss. This study highlights its potential as a safe and effective therapeutic agent for preventing metastatic melanoma.
Area of Science:
- Oncology
- Pharmacology
- Cancer Metastasis Research
Background:
- Melanoma is an aggressive cancer with poor survival rates.
- αvβ3 integrin plays a role in malignant melanoma progression.
- Targeting αvβ3 integrin may offer a strategy to prevent melanoma metastasis.
Purpose of the Study:
- To evaluate the efficacy of MK-0429, a selective αvβ3 integrin inhibitor, in preventing melanoma lung metastasis.
- To assess the safety profile of MK-0429 in a preclinical mouse model.
Main Methods:
- Murine B16F10 melanoma cells were used to induce lung metastases in female B6D2F1 mice.
- Mice were treated with vehicle, MK-0429 (100 and 300 mg/kg), or cyclophosphamide.
- Bioluminescent imaging and ex vivo colony counting were used to quantify metastasis.
Main Results:
- MK-0429 significantly reduced the number of lung metastatic colonies (up to 64%) and tumor area (up to 60%).
- MK-0429 treatment did not cause significant weight reduction in mice, unlike cyclophosphamide.
- Bioluminescent imaging showed reduced progression of lung metastases with MK-0429 treatment.
Conclusions:
- MK-0429 demonstrated safety and efficacy in reducing melanoma lung metastasis in mice.
- The findings support the potential of MK-0429 as a novel therapeutic agent for preventing metastatic melanoma.
