Nat Med: First evidence suggests genetic influences cancer metastasis

Introduction: Many cancer patients in their own body cancer cells have spread, must be crying without tears, the heart will most lying, why is I? Why am I so unlucky? How did a good cancer spread? Doctors have never had an accurate answer, suggesting that Aimo can helpResearchers in order to patients to take great pains, and finally the emperor is not responsible for the people, a bright lamp appeared! They have long wondered whether cancer metastasis is an unspeakable secret to genetic mutations, and now they have finally caught the handle, quickly with the small board of onlookers to eat melon bar!Recently, scientists at Rockefeller University in New York have conducted animal and human studies that have obtained evidence for the first time that a person's original genetic composition may affect the likelihood of cancer progression and metastasisThe findings could change the way scientists think about cancer metastasis and help provide a basis for treatment decisions by better understanding the risks of patientsThe study was published in the journal Nature MedicineBackground
how do cancer cells generally metastasize? This is done when cancer cells escape the original tissue and build new tumors in other parts of the bodyMost cancers die as a resultPreviously, scientists suspected that the ability to metastasize may be related to genetic mutations, but have yet to find evidence of genetic changes that promote metastasissenior attending physician Sohail Tavazoie and members of his laboratory, who have previously studied the link between the APOE gene and the spread of melanomaThe gene produces a protein that appears to interfere with many processes of cancer cell metastasis, such as the formation of blood vessels, growth deep into healthy tissue, and the ability to block attacks on anti-cancer immune cellshumans carry three different versions of APOE, known as APOE2, APOE3 and APOE4Gene products may differ by only one or two amino acids, but they show different binding and activation to APOE receptors and represent the main risk regulator for certain diseasesIt is worth noting that the APOE4 variant is the largest single gene risk factor for Alzheimer's disease, while APOE2 is protectiveIn addition, the APOE variant regulates other inflammatory-related pathology, including atherosclerosis However, the potential link between the APOE genotype and cancer outcomes remains inconclusive Benjamin Ostendorf, a clinical scientist at the laboratory , believes the APOE mutation could explain why melanoma progresses differently in different populations the process and results researchers conducted a series of experiments in melanoma mice carrying human variants of the APOE gene The results showed that tumors in animals with APOE4 grew at a slower rate and spread less well than mice with APOE2 variants A more detailed analysis shows that APOE4 is the most effective version of APOE in terms of enhancing the immune response to tumor cells In mice with APOE4, large amounts of anti-cancer T-cells were clustered to melanoma and blood vessels were reduced, compared to mice with other variants when researchers analyzed immune cells in tumors and grouped them by type, they found that APOE4 mice had more anti-cancer cells genetic data from more than 300 human melanoma patients were similar to those in mouse experiments The researchers first studied the aPOE mutation in the reproductive cells of melanoma patients in the cancer gene database They found that the status of APOE carriers was significantly correlated with survival rates But surprisingly, the status of APOE carriers is significantly correlated with survival rates The median survival of APOE2, APOE3 and APOE4 carriers was 2.4, 5.2 and 10.1 years, respectively these data show that the APOE genotype regulates the abundance and functionalstate of the tumor immune microenvironment, and that the APOE4 variant causes enhanced anti-tumor immune properties compared to the APOE2 variant The researchers believe that the main effect of APOE changes is due to differences in the way they regulate immune system attacks then the researchers confirmed their findings in another group of patients diagnosed with primary melanoma The combined results showed that, on average, patients with APOE4 had the longest survival time, while those with APOE2 had the shortest survival time These findings suggest that it is possible to assess the risk of cancer progression in future by looking at the genes of melanoma patients these findings may also affect the course of treatment Other studies in melanoma mice have shown that APOE mutations affect the success of immunotherapy After anti-PD1 treatment, APOE4 mice survived significantly longer than APOE2 mice, suggesting that the APOE genotype could regulate the outcome of melanoma even in immunotherapy analysis of human melanoma patient data treated with anti-PD1 checkpoint inhibition after progression in anti-CTLA4 treatment also showed that individuals with APOE4 variants responded better to treatment APOE4 and APOE2 carriers in the study also showed the longest and shortest survival results, respectively in the last set of experiments, the team investigated whether pharmacologically increasing APOE production affected the survival of melanoma They showed that the experimental compound RGX-104, which increased APOE yield, helped a variant of APOE4 to fight tumors In general, , the researchers found that mice with APOE4 variants were less likely to be metastatypes than mice with a form of APOE2, had longer survival times and responded better to immunocheckpoint therapy Analysis of data from human cohorts similarly showed an improvement in the survival of melanoma patients with APOE4 variants compared to those with APOE2 These genetic variants may have the same effect on other types of cancer meaning and future planning this study provides evidence of a causal link between their role in neurodegenerative diseases, and that the highly prevalent APOE4 and APOE2 variants produce beneficial and undesirable progressions in melanoma by affecting anti-tumor immunity This finding has several potential clinical implications Most importantly, common variants can act as biomarkers to identify patients with high risk of metastatic recurrence and melanoma-related deaths for assisted systemic therapy researchers say they found that they needed to be repeated in prospective studies It is also important to assess the effect of APOE genotypes on different types of cancer outcomes More generally, their findings support the idea that genetic variants in the same gene can positively or negatively affect future progression and survival outcomes, as well as the therapeutic response to malignant tumors in humans in general Tavazoie suggests that further research is needed to determine how to optimize treatments for patients with other APOE variants For example, APOE2 is associated with increased risk of transfer, while evidence to date suggests that APOE3's ability to suppress transfer is somewhere between the other two variants They need to find patients whose genes put them at risk of poor survival and determine which treatment is best for them , the effects may exceed cancer Contrary to its apparent inhibition of cancer progression, APOE4 was associated with an increased risk of Alzheimer's disease It is not clear how APOE plays a role in Alzheimer's disease, but they believe their work on cancer could also improve understanding of the disease Tavazoie's lab, which usually focuses on cancer, has begun to study its relationship to neurodegenerative diseases