Public and philanthropic research funding, publications, and research networks for cancer in the Commonwealth and globally between 2016 and 2023: a comparative analysis.

This Review presents a comprehensive analysis of the amounts and distribution of public and philanthropic global cancer research funding between 2016 and 2023, including patterns of international collaboration and downstream research output, with an emphasis on the Commonwealth. We show that annual investment decreased globally each year, apart from a rise in 2021. Network analysis revealed that grant and publication collaborations between the Commonwealth, the USA, and the EU are facilitated by linkages through a core group of Commonwealth countries, including the UK, Australia, and Canada.

Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing.

Obesity is associated with worse breast cancer outcomes and decreased therapeutic efficacy. However, the mechanisms driving obesity-associated therapy resistance remain unclear; in part due to a lack of suitable models that recapitulate the obese tumour microenvironment. To address this, we developed a 3D in vitro model of obesity-associated breast cancer, to investigate biological mechanisms and to use as a drug testing tool.

Surgical outcomes of neoadjuvant endocrine treatment in early breast cancer: meta-analysis.

Background: Neoadjuvant endocrine therapy presents an important downstaging option with lower toxicity than neoadjuvant chemotherapy in oestrogen receptor (ER)-positive early breast cancer. Meta-analysis of the effects of neoadjuvant endocrine therapy on surgical outcomes across randomized clinical trials (RCTs) and cohort studies has not previously been performed.

Methods: A systematic review and meta-analysis was performed to evaluate the effect of neoadjuvant endocrine therapy on surgical outcomes (PROSPERO (international prospective register of systematic reviews, 2020)) compared with surgery followed by adjuvant endocrine therapy.

Obesity Is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue whose primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear.

Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma.

Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer the presence of CLS has been correlated to high body mass index (BMI), larger mammary adipocyte size and postmenopausal status. However, the prognostic significance of CLS in HER2 + breast cancer is still unknown.

Werner Syndrome Protein Expression in Breast Cancer.

Introduction: Werner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), which is characterized by premature aging and cancer predisposition. Malignancies that are commonly linked to WS are thyroid carcinoma, melanoma, breast cancer, meningioma, and soft tissue and bone sarcomas.

Oncogenic osteomalacia and metastatic breast cancer: a case report and review of the literature.

Objectives: Oncogenic osteomalacia is a rare paraneoplastic metabolic syndrome that is characterised by severe hypophosphataemia, hyperphosphaturia and osteomalacia secondary to renal loss of phosphate. It is commonly caused by overproduction of fibroblast growth factor-23 (FGF23) from benign tumours of mesenchymal origin. Currently, there is no clear evidence on the management of oncogenic osteomalacia in patients with metastatic solid tumours.

Breaking the cycle: Reversal of flux in the tricarboxylic acid cycle by dimethyl fumarate.

Objective: To infer molecular effectors of therapeutic effects and adverse events for dimethyl fumarate (DMF) in patients with relapsing-remitting MS (RRMS) using untargeted plasma metabolomics.

Methods: Plasma from 27 patients with RRMS was collected at baseline and 6 weeks after initiating DMF. Patients were separated into discovery (n = 15) and validation cohorts (n = 12).

Clinicopathological significance of ataxia telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3-related (ATR) kinase in MYC overexpressed breast cancers.

Purpose: MYC transcription factor has critical roles in cell growth, proliferation, metabolism, differentiation, transformation and angiogenesis. MYC overexpression is seen in about 15% of breast cancers and linked to aggressive phenotypes. MYC overexpression also induces oxidative stress and replication stress in cells.

The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response.

Background: Cyclin-Dependent Kinases (CDKs) are established anti-cancer drug targets and a new generation of CDK inhibitors are providing clinical benefits to a sub-set of breast cancer patients. We have recently shown that human CDK18 promotes efficient cellular responses to replication stress. In the current study, we have investigated the clinicopathological and functional significance of CDK18 expression levels in breast cancers.