A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED).

Objective: Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC).

Methods: Eligible patients with mBC were treated with nab-paclitaxel (100mg/m) weekly for 3 weeks with one week break in a 28-day cycle.

Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer.

Background: Resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether the benefit is consistent for BRAF V600E mutant (MT) and wild type (WT) mCRC. This retrospective analysis explores the influence of BRAF MT on survival after metastasectomy.

Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch.

Lysine specific demethylase 1 (LSD1) is a key epigenetic eraser enzyme implicated in cancer metastases and recurrence. Nuclear LSD1 phosphorylated at serine 111 (nLSD1p) has been shown to be critical for the development of breast cancer stem cells. Here we show that circulating tumor cells isolated from immunotherapy-resistant metastatic melanoma patients express higher levels of nLSD1p compared to responders, which is associated with co-expression of stem-like, mesenchymal genes.

Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer.

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations.

Rate of cancer progression as a predictive marker of efficacy of immunotherapy; an analysis in metastatic non-small-cell lung cancer.

To explore the value of rate of cancer progression (ROP) prior to starting PD-1 inhibitors as a predictive and prognostic biomarker. Retrospective data of patients with metastatic non-small-cell lung cancer treated with second-line PD-1 inhibitors were collected. Patients were divided into two groups: slow and rapid based on their ROP.

Optimise not compromise: The importance of a multidisciplinary breast cancer patient pathway in the era of oncoplastic and reconstructive surgery.

Modern breast cancer care is a complex multidisciplinary undertaking in which the integrated function of multiple constituent parts is critical, and where changes to one therapeutic component may profoundly influence the delivery and outcomes of another. Oncoplastic and reconstructive breast surgery has evolved in the era of longer survival rates for women with breast cancer and aims to enhance oncological and cosmetic outcomes. However, concurrently there has been an expansion in the indications for post-mastectomy radiation therapy (Abdulkarim et al.

Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic and immunotherapy.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor survival outcomes. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune-directed therapies for other solid organ malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective anticancer drugs that produce good initial clinical responses, especially in homologous recombination DNA repair-deficient cancers.

The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern.

Background: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis.

Methods: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases.

Dose modifications in adjuvant chemotherapy for solid organ malignancies: A systematic review of clinical trials.

Toxicities of systemic cancer therapies are often less frequently observed in clinical trials than in clinical practice, due to the careful selection of patients with fewer comorbidities. Although guidelines exist for the estimation of chemotherapy dose, clinical factors like age, comorbid illness and extremes of body habitus are not considered in the method of dose calculation, which can result in significant toxicity. We reviewed the referenced clinical trials from which the evidence-based curative-intent cancer treatment protocols were developed for EVIQ, which is an Australian government, online resource.

Isolated immune-related pancreatic exocrine insufficiency associated with pembrolizumab therapy.

We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis.

Intravesical Gemcitabine versus Intravesical Bacillus Calmette-Guérin for the Treatment of Non-Muscle Invasive Bladder Cancer: An Evaluation of Efficacy and Toxicity.

Background: Intravesical Bacillus Calmette-Guérin (BCG) remains the standard adjuvant treatment for non-muscle invasive bladder cancer (NMIBC) following transurethral resection; however, BCG failure and related toxicities are common.

Objectives: To compare the efficacy and toxicity of intravesical BCG and gemcitabine in the treatment of NMIBC.

Methods: Retrospective data were collected in the region of Canberra, Australia from January 2010 to December 2015.

Massive fatal pulmonary haemorrhage during bevacizumab treatment following microwave ablation therapy for oligometastatic lung metastasis from rectal cancer.

Although thoracic ablative therapies are generally safe procedures, fatal complications can occur. Bevacizumab is a standard-of-care treatment along with chemotherapy for metastatic colorectal cancer. Although uncommon, unpredictable serious adverse events can occur secondary to bevacizumab.