New progress in cancer drug resistance research!

In this paper, several research reports were compiled to interpret the new achievements of scientists in the field of cancer drug resistance research! Share with you! Photo source: nepron / Wikipedia [1] PNAs: extremely active FoxA1 signal or breast cancer with reprogramming endocrine resistance makes it more aggressive doi: 10.1073/pnas.1911584116 recently, an international journal Proceedings of the National Academy of In the Research Report on sciences, scientists from Baylor medical college found a new mechanism through research, which may help to explain the mechanism of endocrine resistant breast cancer to obtain metastasis characteristics Relevant research results may help scientists develop new breast cancer therapy The researchers pointed out that the extremely active FoxA1 signal may induce the whole genome reprogramming, and lead to the increase of cancer cells' resistance to therapy and metastasis behavior Previously, researchers found the extremely active FoxA1 signal in the endocrine resistant metastatic breast cancer The researchers found that HIF-2a may be a key mediator for FoxA1 directed reprogramming, while HIF-2a inhibitors (currently used to treat advanced renal cell carcinoma and recurrent glioblastoma) can selectively reduce the metastasis of cancer cells and the invasion of endocrine resistant breast cancer cells with high FoxA1 activity 【2】 Nat Med: liquid and tissue biopsy to detect acquired drug resistance and tumor heterogeneity of gastrointestinal tumors doi: 10.1038/s41591-019-0561-9 in the process of cancer treatment, tumor heterogeneity can drive the evolution of multiple tumor subclones, which have unique drug resistance mechanism in different patients Previous case reports and small case series studies have shown that liquid biopsies (especially cell-free DNA, cfdna) can better reveal the heterogeneity of sexual drug resistance However, up to now, there is no study comparing cfdna with standard single focus tumor biopsy directly in large-scale prospective patient population after the progress of targeted therapy Recently Ryan B Corcoran from Harvard Medical School and Massachusetts General Hospital, in collaboration with GAD Getz of MIT and Harvard broad research institute, conducted a prospective study in 42 patients with gastrointestinal cancer defined by molecular detection and targeted treatment of acquired drug resistance He directly compared the cfdna and tumor after development The results show that cfdna can more accurately determine the clinical resistance changes and multiple resistance mechanisms in 78% of patients without changes detected by liquid biopsy 【3】 Mol Cancer Res: overcome the drug resistance of pancreatic cancer The combination of new drugs makes the king of cancer bow his head and admit doi: 10.1158/1541-7786.mcr-19-0589 pancreatic cancer is one of the most deadly cancers Once the disease spreads, the average survival of patients is less than one year At present, there is an urgent need to evaluate more treatment targets The chemotherapy drug abemaciclib is effective in the treatment of breast cancer, but there is little pre clinical evaluation of the drug targeting the treatment of pancreatic cancer A new study by the Sidney Kimmel Cancer Center Jefferson health (skcc) provides evidence to support the use of abemaciclib in pancreatic cancer, and proposes new goals to improve the efficacy of the drug and break the common drug resistance problem in the disease The study was recently published in the journal Molecular Cancer Research We don't know how abemaciclib works against pancreatic cancer, or how it can be used in combination with other drugs to improve its efficacy, the researchers said To study the mechanism of this drug, the researchers evaluated the role of abemaciclib in pancreatic ductal adenocarcinoma cell line They found that the drug can cause cell death and prevent cell growth Compared with the control group, the tumor growth rate of mice treated with drugs decreased Abemaciclib targets enzymes that regulate cell division However, these enzymes only work when combined with another group of enzymes 【4】 Nature: resistance to breast cancer may be related to leucine rich diet! Doi: 10.1038/s41586-019-1126-2 about one eighth of American women will develop breast cancer in their lifetime Most breast cancers rely on estrogen to grow Estrogen receptor positive (ER +) breast cancer is often treated with tamoxifen, a drug that blocks the effects of hormones on tumors However, many tumors eventually develop resistance to tamoxifen, which leads to cancer recurrence or metastasis Now, a team of researchers at the Beth Israel Deaconess Medical Center (bidmc) cancer center have found an unexpected relationship between leucine levels and the development of tamoxifen resistance in ER + breast cancer Under the leadership of Dr senthil K muthuswamy, the researchers further identified a key protein that can transfer leucine into cells and regulate the sensitivity of ER + breast cancer cells to tamoxifen The relevant research results were recently published in nature This study revealed a potential new strategy to overcome the endocrine drug resistance of ER + breast cancer patients 【5】 Iscience: revealing the mechanism of chemotherapy tolerance related to p53 doi: 10.1016/j.isci.2020.100820 In the world, more than half of cancer cases are related to the mutation of p53 gene The protein produced by it can protect DNA from inducing cancer changes When the protein is deformed, it will not only lose its protection ability, but also produce new functions It will play the role of "traitor", and promote tumor by forming protein clusters that may be resistant to chemotherapy At present, researchers are not clear about the mechanism of this situation and how it produces drug resistance Recently, in a research report published in the International Journal iscience, scientists from Brazil's National Institute of structural biology and biological imaging science and Technology identified a large number of "traitor" egg whites in the chemoresistant cells derived from glioblastoma, and researchers revealed how these proteins deform to resist therapy, which can form a ratio of In this study, for the first time, researchers observed these changes in the nucleus of living cells Photo source: Hokkaido University [6] oncogene: new drug combination may prevent resistance to melanoma treatments Recently, in a research report published in the international journal oncogene, scientists from Michigan State University found that a new combination of drugs can effectively inhibit the tolerance of melanoma to treatment, which is a fatal skin cancer; relevant research results may help to effectively treat about half of the melanoma with drug tolerance Patient The researchers found that about half of drug-resistant melanoma showed activation of the signal pathway involving Rho protein The results showed that the combination of the drug verofinil with another compound interfering with Rho signal can make cancer cells sensitive to therapy again In this paper, the researchers identified a clinically approved drug and three investigational compounds that can enhance the response of drug-resistant melanoma to verofinil, one of which can eventually be used for clinical use 【7】 Neuro oncology: to identify a new compound doi: 10.1093/neuronc/noz170, which can effectively kill cancer cells resistant to chemotherapy Recently, in a research report published in the international journal neuro oncology, scientists from Hokkaido University and other institutions have identified a special compound that can effectively kill glioblastoma initiating cells (GICs) that are resistant to chemotherapy through research The relevant research results may help to develop a radical treatment of refractory tumors Low toxicity drugs Although scientists have been trying to develop new treatment methods for a long time, the prognosis of most patients with glioblastoma undergoing chemotherapy and radiotherapy is still poor Glioblastoma is a kind of malignant glioma The median survival of patients is only about 15 months left and right One of the reasons for the short median survival of patients is the lack of elimination of cancer stem cells Or GICs, and these cells often show certain tumorigenic characteristics and tolerance to chemotherapy and radiotherapy 【8】 Cancer cell: how can scientists effectively solve the problem of tolerance of cancer patients to immunotherapy? Doi: 10.1016/j.ccell.2019.08.008 recently, in a research report published in the international journal Cancer Cell, scientists from the University of Melbourne and other institutions studied human cancer and facial tumors of Tasmanian devils The discovery of a class of active interacting proteins may help to explain why cancer evades the attack of the immune system The relevant research results are expected to help develop new drug combinations to improve the effectiveness of cancer immunotherapy In this paper, the researchers analyzed why some cancer cells lose special proteins from their surface and promote cancer cells to evade the attack of the host immune system; they found that when the protein complex named PRC2 is in an overactive state, cancer cells will lose the ability to present class 1 MHC protein, and the expression of class 1 MHC protein can be used by the host immune defense system Recognition is crucial What's more interesting is that the loss of class I MHC protein in facial tumors of Tasmanian devils may be caused by the same process 【9】 SCI transl Med: scientists are expected to develop a new strategy to overcome the cancer drug tolerance of cancer cells Doi: 10.1126/scitraslmed.aaw8828 recently, an international journal Science Translational In the Research Report on medicine, scientists from institutes such as the National Institutes of health of the United States designed a potential therapy to resist common types of leukemia, which may have some significance for the treatment of other types of cancer; this new method aims to target the effect of cancer cells to avoid drug efficacy, that is, adaptive resistance of cancer cells resistance）。 In this paper, the researchers identified a special cell pathway that can promote the avoidance of drugs in acute myeloid leukemia (AML) Then they designed a compound to attack cancer cells doubly In many experiments, the compound can block the function of the mutant protein that induces AML, and at the same time, it can inhibit the avoidance of compounds in cancer cells With the ability of effect, the relevant research results are expected to help researchers develop new therapies for AML 【10】 Clin Cancer Res: special kinase or can regulate the tolerance of ovarian cancer to platinum based therapy doi: 10.1158/1078-0432.ccr-18-4145 recently, a research report published in the international journal Clinical Cancer Research, scientists from George Washington University found that ERK, extracellular regulated The specific protein of kinase may play a key role in the tolerance of ovarian cancer to platinum therapy Relevant studies provide clinical evidence for the first time to confirm the relationship between ERK and HIF-1 α (hypoxia inducible factor)