Ileal apoptosis and microbiota mediate colon cancer treatment efficacy

A recent study sheds further light on the interdependent relationship between the intestinal epithelium, the intestinal microbiome and host immunity, and their combined influence on homeostasis and disease.

Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerisation

Scientists have demonstrated that normal tissue from the tumour harbouring breast is epigenetically different from normal tissue of the opposite breast despite histology appearing normal in both cases.

Heterogeneous components of lung adenocarcinomas harbour distinct EGFR mutations and PD-L1 expression

A recent study using laser capture microdissection demonstrated that different areas of the same lung adenocarcinoma tissue can harbour both sensitising EGFR mutations and those mutations that confer resistance to TKIs.

ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumour activity following irradiation

Authors of a recent study have shown that the ATR kinase inhibitor combined with local tumour radiation generated a durable CD8+ T cell-dependent anti-tumour response.

In vivo selection reveals autophagy promotes adaptation of metastatic ovarian cancer cells to abdominal microenvironment

An increase in autophagic potency among ovarian cancer cells may be crucial for selection of metastatic colonies in the abdominal microenvironment. Autophagy may be a promising potential therapeutic target in the treatment of ovarian cancer.

Identification of a Radiosensitivity Molecular Signature Induced by Enzalutamide in Hormone-sensitive and Hormone-resistant Prostate Cancer Cells

Androgen Deprivation Therapy (ADT) has demonstrated improved clinical success with further anti-tumour efficacy when combined with XRT, however, half of patients develop a resistance. In this study the authors identified potential prognostic biomarkers for response to combined ENZA, ADT and XRT therapy.

Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy

Prophylactic TNF blockade may safely allow doses of ipilimumab to be increased in immune checkpoint blockade combined therapies.

Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy

To discover potential biomarkers of response and resistance to anti-PD1 monotherapy and combined anti-PD1/anti-CTLA-4 immunotherapies in a cohort of melanoma patients.

Epithelial-mesenchymal transition in human prostate cancer demonstrates enhanced immune evasion marked by IDO1 expression

Cancer invasion and metastasis are driven by epithelial-to-mesenchymal transition (EMT). This study identifies an important link between EMT and immune evasion in prostate cancer patients.

Transcriptomic analysis of hepatocellular carcinoma reveals molecular features of disease progression and tumour immune biology

Hepatocellular carcinoma (HCC) is a common cause of cancer deaths with a particularly poor prognosis. A recent publication by Okrah et al., describing molecular aspects of HCC progression illustrates the power of multigene transcriptomic signatures suggesting a rationale for immunotherapy early in HCC disease progression and potentially in combination with an anti-fibrotic strategy.

Acute Lymphoblastic Leukaemia highjacks a neural mechanism to invade the CNS

Acute Lymphoblastic Leukaemia (ALL) most often metastasise to organs such as the spleen and lymph nodes, but also to the Central Nervous System (CNS). Here, Yao et al show that ALL cells infiltrate the CNS not by breaching the blood-brain barrier, but by hijacking the neural migratory pathways.

Determinants of variability of five programmed death ligand-1 immunohistochemistry assays in non-small cell lung cancer samples

Upregulation of PD-L1 is associated with increased risk and tumourigenicity of cancers, helping many escape immune surveillance. PD-1/PD-L1 expression has been suggested as a possible biomarker for identifying patients that may be sensitive to PD1/PD-L1 immunotherapies. Current PD1/PD-L1 testing procedures may not be sufficient to distinguish responders and this study aimed to simplify the process by assessing the different methods on clinically-relevant NSCLC samples, to identify factors relevant for PD-L1 detection and make assays more robust and reproducible.

Gene expression profiles from plucked scalp hair to assess pharmacodynamic biomarkers following treatment of advanced solid tumors with a novel anti-cancer stem cell Wnt inhibitor

Wnt signaling pathway genes are crucial for cell fate determination and cell polarity during development. Ipafricept (OMP-54F28) is a first in class recombinant fusion protein producing a truncated decoy receptor that binds to a cystine-rich region of Wnt ligand and as a result it blocks the activation of the Wnt signaling. Here the authors described the results of a phase 1 first in-human clinical trial.

Two recent papers highlight the importance of tumour microenvironment on cancer cell stemness

Two recent papers demonstrate the importance of the tumour microenvironment on its progression through in vitro co-culture. The authors in one paper show that M2 macrophages increase the stem cell capacity of an ovarian cancer cell line, whilst in the other fibroblasts increase the stemness of a lung carcinoma cell line. They highlight the importance of considering the tumour microenvironment in in vitro experimentation, and also reveal potential new therapeutic targets.

CAR-T Cells in cancer Therapy

Summary of a paper reporting an unusually delayed response from one patient during a clinical trial in CLL using CAR T-cells targeted to CD-19 that may shed light on some of the mechanisms determining persistence of CAR T-cells and their clinical outcome.

4PD1hi cells predict response to immunotherapy

An interesting paper published in Cancer Cell explores the role of a newly identified and non-conventional subset of inhibitory CD4+ T cells.

Can changes to gut microbiota affect the efficacy of chemotherapies?

Can changes to gut microbiota affect the efficacy of chemotherapies?

Oncogenic JAK2V617F causes PD?L1 expression, mediating immune escape in myeloproliferative neoplasm

Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms

Targeting breast cancer with Hsp70?aptamer?guided nanoparticles with chemotherapeutic payloads

Targeting breast cancer with Hsp70-Aptamer-guided nanoparticles with chemotherapeutic payloads

CAR-T Cells: Engineering Immune Cells to Treat Cancers

For many years surgery, chemotherapy and radiation therapy have been the foundations of cancer treatment. Over the last two decades, targeted therapies have cemented themselves as standard treatments for many cancers and over the past several years, immunotherapy therapies that enlist and strengthen the power of a patient’s immune system to attack tumours has emerged.

Stratification of Patients using Gene Expression Analysis of Laser Capture Microdissected (LCM) Tissue and Histology/IHC

This procedure could help stratify patients where pre-treatment could be avoided, these patients may then benefit from advanced surgery or alternative treatment options and prevent unnecessary toxicities.

JAK2, a novel therapeutic target in lung adenocarcinoma?

The field of personalised medicine to provide understanding of the molecular basis of disease is constantly growing. Multiple signalling pathways have been identified that associate with malignant transformation. However, the vast majority of lung cancer patients have no known driver genes detected, and they are still treated with standard cytotoxic chemotherapy.

Platelets are major suppressors of T cell function

We currently offer validated models to address immune function in tumour bearing mice. Our detailed flow cytometric expertise can further assess the identity of tumour infiltrating and peripheral cell populations such as CD8+ T cells, MDCSs and regulatory T cells, by surface identification of key molecules, or the intracellular mediators they express (cytokines, transcription factors).

Development of a Signature of Aberrant Myc Transcription has Prognostic Value in Evaluating Novel Myc-Targeted Therapies

Altered expression of transcription factors are key indicators in cancer progression in functions such as proliferation and differentiation, angiogenesis and apoptosis. A significant proportion of cancers are driven by mutations in these networks, including Wnt/?-catenin, Ras/MAPK and Myc

New biomarker/therapeutic target in AML

The field of personalised medicine to provide understanding of the molecular basis of disease and the mechanism of action of chemotherapeutic drugs is constantly growing. A recent study carried out by Schneider et al has highlighted several interesting facts.

The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

We currently offer 3 models to address the immune response in tumour bearing mice. Metabolic and mitochondrial function of T cells can be assessed by flow cytometry. Our detailed flow cytometric expertise can further assess the identity of tumour infiltrating and peripheral cell populations, by surface identification of key molecules, or the intracellular mediators they express (cytokines, transcription factors).

Novel drug prevents AML cells from hiding