Metastasis occurs when the cancer cells escape the original tissue and establish new tissue elsewhere. Most cancer deaths are caused by this phenomenon and previously, most research has looked for mutations in the cancer progression that enables them to travel. A new study is the first to find a genetic variant that is inherent that could encourage metastasis
The study, published in Nature on Monday, suggested that alleles in a single gene can alter the progression of melanoma, a type of skin cancer. The researchers went on to suggest that they suspect that these inherited variations may have the same effect on other cancers as well.
ApoE4 and ApoE2 are genes that are known to be associated with Alzheimer’s disease, but in the opposite way to its effect on Alzheimer’s, they confer to favourable and poor outcomes in melanoma respectively. The study tested mice expressing the human ApoE4 and showed they had reduced melanoma progression and metastasis relative to ApoE2 mice. They also found that ApoE4 is the most effective version of the gene in enhancing the immune response to tumour cells.
They then looked at the genetic data from melanoma patients, which echoes the mouse experiments: people with the ApoE4 variant survived the longest while those with ApoE2 survived the shortest. This suggests that doctors could look at a patient’s genetics to assess their likelihood of cancer progression and metastasis, which could influence the course of treatment. Melanoma patients are often given immunotherapies to encourage their immune systems to fight cancer and as patients with the ApoE4 variant respond best to immune-boosting therapies, this could influence who receives this type of treatment.
The lead investigator, Sohail Tavazoi states that doctors now have an answer to patients that ask why their cancer spread. Previous research in his lab identified the APOE gene that can impact the spread of melanoma. The gene produces a protein that appears to interfere with several processes that cancer cells use to metastasise, such as angiogenesis, growing deeper into healthy tissue and withstanding assault from immune cells.
Humans carry one of three versions of ApoE: ApoE2, ApoE3 and ApoE4. Benjamin Ostendorf, a physician-scientist in the lab has hypothesised that these variants could explain why melanoma progresses differently among patients.
As the ApoE4 gene is associated with Alzheimer’s progression, Tavazoie says that although it is not quite clear how the ApoE gene affects Alzheimer’s, their work in cancer could inform our understanding of this disease as well. As a result, his lab which is normally focused on cancer has started to investigate the connection between the gene and the neurodegenerative disorder.