Study Rationale:
People with Parkinson's disease (PD) are more likely to develop melanoma, and people with melanoma are more likely to develop PD than the general population. Additionally, melanoma tumors often show spontaneous mutations in genes known to increase risk for PD, with those in LRRK2 being the most common. This study will compare melanoma development and metastasis in control models and models carrying a mutation in LRRK2 (G2019S) that is the most commonly observed in PD patients.
Hypothesis:
We hypothesize that LRRK2 mutation will promote tumor growth and metastasis by its actions in immune cells.
Study Design:
The first goal is to measure, compare and characterize tumor growth and metastasis in models expressing a LRRK2 G2019S mutation. Because LRRK2 is enriched in immune populations and its mutation is associated with altered immune responses, the second aim is to identify, quantify and compare immune cell populations in spleen and infiltrating tumors in LRRK2 G2019S and control models. The final aim will test whether LRRK2 kinase inhibition can reverse key phenotypes identified.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Onset of melanoma commonly precedes development of PD. It is possible that tailored treatments aimed toward mitigating cancer risk may also mitigate PD risk.
Next Steps for Development:
If the data show that LRRK2 mutation alters immune cell responses to melanoma in models, the next step would be to replicate these findings in human samples and to test the effectiveness of LRRK2 inhibition.