Category Archives: Cancer Types

BRD4 controls Long noncoding RNAs to regulate glioblastoma proliferation

Long non-coding RNAs (lncRNA) are non-protein coding transcripts longer than 200 nucleotides. They have been looked as rubbish of the transcripts before, however, recently study indicate that they play critical roles in cancer initiation and malignant progression. FDA has approved five epigenetic drugs for use in cancer treatment: two DNA methyltransferase (DNMT) inhibitors and three histone deacetylase (HDAC) inhibitors. BET bromodomain inhibitors exert a broad spectrum of desirable biological effects such as anticancer and anti-inflammatory properties.

BRD4 controls Long noncoding RNAs to regulate glioblastoma proliferation

Firstly, we profile lncRNAs differentially expressed in GBM. We have analyzed the RNA sequencing data by testing expression of each annotated transcript in each individual GBM sample compared against all normal samples.

Next, knockdown of HOTAIR causes apoptosis and reduces the proliferation of glioblastoma cells in vitro and in vivo.

Finally, Treatment of GBM cells with the BET bromdomain inhibitor I-BET151 reduced levels of the tumor-promoting lncRNA HOX transcript antisense RNA (HOTAIR) and restored the expression of several other GBM down-regulated lncRNAs. BRD4 bind to the HOTAIR promoter, suggesting that BET proteins can directly regulate lncRNA expression.

To summary, we have identified a mechanism that small molecule inhibitors of BET bromodomain proteins reduce expression of several oncogenes required for GBM progression.

Scientists Found Fatal Weakness of Brain Cancer Stem Cells

Researchers from Washington University School of Medicine, St.Louis have discovered that even for brain cancer stem cells exist fatal weakness. Two important protein, SOX2 and CDC20, play key role in remaining the characters in brain cancer stem cells. This study was published in Cell Reports.

Scientists Found Fatal Weakness of Brain Cancer Stem Cells

Glioblastoma, the most common malignant primary tumor in adults, remain a challenging disease with a poor prognosis. Increasing appreciation of the cancer cell heterogeneity within glioblastomas has focused attention on a subpopulation of cells called tumor-initiating cells or glioblastoma stem-like cells (GSCs).

The anaphase-promoting complex (APC) E3 ubiquitin ligase functions with co-activator CDC20 to drive mitosis. CDC20-APC has been viewed as a potential strategic target in several human cancers. CDC20 mRNA is elevated in glioblastoma compared to low-grade gliomas, and CDC20 immunoreactivity in gliomas correlates with pathological grade, but little is known about the biological roles of CDC20-APC in glioblastoma.

In this study, researchers report CDC20-APC is required for GSC invasiveness and self-renewal in a manner distinct from its role in cell-cycle control. They identify pluripotency-related transcription factor SOX2 as a CDC20-interacting protein and show CDC20-APC operates through SOX2 to regulate human GSC in invasion and self-renewal. Finally, they demonstrate that CDC20-APC is essential for GSC tumorigenicity in orthotopic xenografts and that CDC20 expression has prognostic value in a subset of glioblastoma patients.


These results highlight a critical role for CDC20-APC in the maintenance of human GSC function, and they suggest that targeting this pathway in glioblastoma may disrupt the GSC state.

Preventing Colon Cancer by Changing Intestinal Flora

Scientists from St.Jude Children’s Hospital have identified one gene that expresses in immune system plays important role in determining the invasiveness of colon cancer. Their study was published in Cell and may play vital role in the prevention, diagnosis, and treatment of colon cancer.

Preventing Colon Cancer by Changing Intestinal Flora

Colorectal cancer is a leading cause of cancer-related deaths, with 160,000 cases being diagnosed annually in the USA. Mutations in the gene encoding AIM2 are frequently identified in patients with colorectal cancer. A previous study has shown that more than 50% of tumors from patients with small bowel cancer have frameshift mutations in the gene encoding AIM2. Further genetic evidence has shown that missense mutations are targeted to coding regions of the gene encoding AIM2 in colon cancer tissues and cell lines. AIM2 is a cytosolic double-stranded DNA receptor that contributes to the host defense against bacterial and viral pathogens.

In this study, researchers found that AIM2-deficient mice developed more tumors in the colon following azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced colitis-associated tumorigenesis. Unlike its role in the host defense against infection, AIM2 protected against tumorigenesis by controlling intestinal epithelial cell proliferation via a mechanism independent of inflammasomes and inflammatory mediators. Upon deregulated Wnt signaling, AIM2 suppressed expansion of tumor-initiating intestinal stem cells lining the base of the crypt.

Remarkbaly, reciprocal exchange of the gut microbiota between healthy WT mice and Aim2-/- mice reduced the susceptibility of Aim2-/- mice to colorectal tumorigenesis. These findings revealed a role for AIM2 and its synergy with gut microbiota in the development of colorectal cancer.

Scientists Found Key Maker of Immune System in Prostate Cancer Patients

Scientists from Cold Spring Harbor have published their new research progress , which prove that how immune system cytokines IL-6 drives invasiveness and play important role in prostate therapy. This study was published on Cancer Discovery.


Prostate cancer(PC) is one of the most prevalent cancers among men and it is estimated that in 2014 there will be 233,000 new PC cases, making up 14% of all new cancer cases , causing an estimated 29,480 deaths in United States alone. Although mortality rates have been decreasing, PC is still among the most common causes of cancers-related death and malignancy in men in developed counties.

In this study, scientists show that cell-cell communication by II6 drives the Akt-Myc switch through activation of the Akt-suppressing phosphatase Phlpp2, when Pten and p53 are lost together, but separately. II6 then communicates a downstream program of Stat3-mediated Myc-activation, which drives cell proliferation. Similarly in tissues, peak proliferation in Pten/ Trp53 mutant primary and metastatic PC does not correlate with activated Akt, but with Stat3/ Myc activation instead. Mechanistically, Myc strongly activates the Akt phosphatase Phlpp2 in primary cells and PC metastasis. They show genetically that Phlpp2 is essential for dictating proliferation of Myc-mediated Aktsuppression。

Collectively, their data reveal competition between two proto-oncogenes: Myc and Akt, which ensnarls the Phlpp2 gene to facilitate Myc-driven PC metastasis after loss of Pten and Trp53.


Nowak D G, Cho H, Herzka T, et al. Myc drives Pten/p53-deficient proliferation and metastasis due to Il6-secretion and Akt-suppression via Phlpp2[J]. Cancer discovery, 2015: CD-14-1113.

Study: High-fat Western diet increases chances of prostate cancer



If you’re one of the nearly 3 million men currently living with a diagnosis of prostate cancer, listen up: Anew study says what you eat makes a big difference as to how long you’ll live with your cancer.

Chavarro and fellow researchers from Harvard T.H. Chan School of Public Health interviewed 926 men with nonmetastatic prostate cancer about their dietary habits over a five-year period. Prostate cancer is frequently slow-growing and nonaggressive and therefore has one of the highest survival rates of any type of cancer.

Two types of eating habits emerged: a “prudent” pattern that included a high intake of fruits, vegetables, whole grains, fish, and beans and other legumes, and a Western pattern made up of processed and red meats, high-fat dairy and refined grains such as often used in processed foods.

The study then followed the men over another 10 years to see how they did. They found men who ate mostly a Western diet of processed and high-fat foods had a 2½ times greater risk of dying from prostate cancer as well as a 67% higher risk of death overall. Men who were “prudent” in their food choices had a 36% lower risk of dying from any cause.

Even though the study followed men over a long period of time, the authors point out some limitations: They did not collect data on pre-diagnosis diets of the men, didn’t track physical activity, and most of the 926 participants were white physicians, which might skew results.”Therefore it is very important that our results are replicated in other studies with more diverse socioeconomic and racial/ethnic backgrounds,” lead author Meng Yang said.

Blocking Cancer Cell “Microenvironment” to the Deterioration of Leukemia

Scientists from NYU Langone Medical Center have revealed a breakthrough on defense leukemia, it may help develop new targeting therapy on leukemia. This study was published on Cancer Cell.


Acute lymphoblastic leukemia(ALL) is the most common of childhood cancers, and 15%-20% of ALL cases are T lineage(T-ALL). A quarter of childhood T-ALL patients relapse within 5 years of treatment and receive a dismal prognosis. Factors predicting poor survival of relapsed childhood ALL patients include T lineage disease and isolated bone marrow involvement, both of which have a less than 25% five-year survival rate.

Increasing evidence suggests that leukemic stem cells actively engage in crosstalk with the bone marrow microenvironment to regulate their proliferation and survival. Similarities between LICs and hematopoietic stem cells(HSCs) have raised the hypothesis that LICs require a specialized microenvironment to survive and that disrupting this niche may be a promising therapeutic strategy.

While much is known about the cell-intrinsic factors that support leukemia progression, little is understood about the role of the microenvironment. T cell acute lymphoblastic leukemia(T-ALL) cells have commonly acquired mutations in pathways downstream of surface receptors that regulate differentiation, survival, and proliferation in response to environmental cues, and it is unknown whether this frees T-ALL from dependence on a putative leukemic niche.

In this study, researchers identify CXCL12-producing vascular endothelial cells as a require component of a T-ALL niche. Moreover, they show that targeting CXCL12/CXCR4 signaling after disease onset dramatically reduces T-ALL burden in murine and xenograft models of disease, suggesting a powerful therapeutic approach for this devastating cancer.


 Pitt L A, Tikhonova A N, Hu H, et al. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance[J]. Cancer cell, 2015, 27(6): 755-768.

New Combination Therapy for Pancreatic Cancer Treatment

Researchers from Virginia Commonwealth university have developed a new therapy by combining a common antibiotic and experimental drug to cure pancreatic cancer. This study was published in Cancer research.


Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer that is predicted to cause almost 40,000 deaths in the United States in 2014. PDAC is faily resistant to most standard therapies and results in a 5-year survival rate of about 4%.

The aggressive nature and dismal prognosis of patients with pancreatic cancer results partly from the plethora of molecular changes that occur during PDAC development, one of which is overexpression of the antiapoptotic proteins of the Bcl-2 family. Cancer cells exploit this overexpression to evade cell death and as a mechanism promoting resistance to diverse chemotherapeutic agents.

Sabutoclax (BI-97C1) is a novel Apogossypol derivative BH3 mimetic. This compound binds to the Bcl-2 antiapoptotic proteins Bcl-2, Mcl-1, BclXL, and Bfl-1. It was originally identified on the basis of its ability to bind Bcl-XL with low to submicromolar binding affinity . Scientists have previously shown that sabutoclax shows efficacy against prostate and colorectal cancers, two cancers that also overexpress antiapoptotic Bcl-2 proteins

In this study, researchers offer evidence of the combinatorial antitumor potency of these agents in several preclinical models of pancreatic cancer. Sabutoclax induced growth arrest and apoptosis in pancreatic cancer cells and synergized with minocycline to yield a robust mitochondria-mediated caspase-dependent cytotoxicity. This combinatorial property relied upon loss of phosphorylated Stat3 insofar as reintroduction of activated Stat3-rescued cells from toxicity. Tumor growth was inhibited potently in both immune-deficient and immune-competent models with evidence of extended survival.

Their results showed that the combination of sabutoclax and minocycline was highly cytotoxic to pancreatic cancer cells and safely efficacious in vivo.

‘Be on alert for bladder cancer’ women advised


Bladder cancer is being missed in women because the symptoms are so similar to a urine infection, warn experts. Public Health England says women should take heed and visit their GP if they have blood in their urine or pain while passing water. While most cases will not be cancer, it is a diagnosis that is easy to miss.

It partly explains why in England, 77% of men with bladder cancer survive for a year after diagnosis, compared to 64% of women, they say. Although more men than women get bladder cancer, women tend to fare worse. Data presented at PHE’s Cancer Outcomes Conference in Belfast show women are more likely have their cancer diagnosed later – and often as an emergency.

They are also at higher risk of having rarer and more aggressive types of tumour. And so PHE wants women to be more vigilant. Checking before you flush is just one simple way to stay alert to the warning signs, they have told BBC Five Live. Sara Hiom, Cancer Research UK’s director of early diagnosis, said: “It can be tempting to put a new symptom down to an innocent cause, or wait for it to happen a few times before seeking help.

“But some signs, such as blood in pee, need to be acted on promptly, by both patients and doctors, even if it just happens the once. Being quicker to spot and act on the signs of bladder cancer and ensuring that women receive the right care and treatment is vital if more women are going to survive this disease.”

In 2013 nearly 2,500 women in England were diagnosed with bladder cancer. In the same year, around 1,500 died from the disease. Smoking is the single biggest risk factor for developing bladder cancer. Occupational exposure to certain chemicals – such as some hair dyes – can also increase a person’s risk.

Antibody Injection Therapy may Provide Long-term Immunoprotection against Cancer

Scientists from Rockefeller University applied a tumor specific antigen model to analyze if passive antibiotic injection could cause the sequential immunoreaction. This study was published in Cell.

Passive administration of anti-tumor antibodies is an important clinical tool for the management of a variety of cancers and generally functions by targeting malignant cells through Fc-receptor for IgG(FcγR)-mediated antibody-dependent cellular cytotoxicity(ADCC) by myeloid effector cells or possibly natural killer (NK) cells. However, anti-tumor mAb treatment can also induce a vaccinal effect, in which mAb-mediated tumor death induces a long-term antitumor cellular immune response.


New technologies have enabled the identification of tumor mutational signatures, some common across multiple cancer types while others are restricted to specific malignacies. Thus, mutation-induced, developmentally restricted, or overexpressed tumor neoantigens are a major
target of tumor-infiltrating lymphocytes in patients

Three activating FcγRs are expressed in mice (mouseFcγRI, mFcγRIII, and mFcγRIV) and humans (hFcγRI,hFcγRIIA, and hFcγRIIIA), and a single inhibitory FcγR, FcγRIIB, is expressed in both species. The cellular outcome of IgG interactions with FcγRs is governed by the affinity of an antibody’s Fc for the specific receptor and the expression pattern of those receptors on effector cells

In this study, to determine how such responses are generated, scientists utilized a murine model of an anti-tumor vaccinal effect against a model neoantigen. They demonstrate that FcγR expression by CD11c+ antigen-presenting cells is required to generate antitumor T cell responses upon ADCC-mediated tumor clearance. Using FcgR-humanized mice, we demonstrate that anti-tumor human (h)IgG1 must engage h FcγR IIIA on macrophages to mediate ADCC, but also engage h FcγR IIA, the sole h FcγR expressed by human dendritic cells (DCs), to generate a potent vaccinal effect. Thus, while next-generation antitumor antibodies with enhanced binding to only h FcγR IIIA are now in clinical use, ideal anti-tumor antibodies must be optimized for both cytotoxic effects as well as h FcγR IIA engagement on DCs to stimulate long-term anti-tumor cellular immunity.


DiLillo D J, Ravetch J V. Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect[J]. Cell, 2015, 161(5): 1035-1045.

Small-Molecule Bcl2 BH4 Antagonist for Lung Cancer Therapy

The BH4 domain of Bcl2 is required for its antiapoptotic function, thus constituting a promising anticancer target. We identified a small-molecule Bcl2-BH4 domain antagonist, BDA-366, that binds BH4 with high affinity and selectivity. BDA-366-Bcl2 binding induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer xenografts derived from cell lines and patient without significant normal tissue toxicity at effective doses. mTOR inhibition upregulates Bcl2 in lung cancer cells and tumor tissues from clinical trial patients.


Combined BDA-366 and RAD001 treatment exhibits strong synergy against lung cancer in vivo. Development of this Bcl2-BH4 antagonist may provide a strategy to improve lung cancer outcome.


Guojing Zhang,Gabriel L.Sica,et al. Small-Molecule Bcl2 BH4 Antagonist for Lung Cancer Therapy [J].Cancer Cell, 2015.04.010.