Artemis and its role in cancer.

Artemis is a key nuclease involved in the non-homologous end joining repair pathway upon DNA double-stranded breaks and during V(D)J recombination. It participates in various cellular processes and cooperates with various proteins involved in tumorigenesis. Its hereditary mutations lead to several pathological conditions, such as severe combined immunodeficiency with radiation sensitivity.

Centrosomes and associated proteins in pathogenesis and treatment of breast cancer.

Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female mortality. The inability to effectively treat advanced and/or treatment-resistant breast cancer demonstrates the need to develop novel treatment strategies and targeted therapies.

Lung-derived soluble factors support stemness/plasticity and metastatic behaviour of breast cancer cells via the FGF2-DACH1 axis.

Patients with triple-negative breast cancer (TNBC) have an increased propensity to develop lung metastasis. Our previous studies demonstrated that stem-like ALDHCD44 breast cancer cells interact with lung-derived soluble factors, resulting in enhanced migration and lung metastasis particularly in TNBC models. We have also observed that the presence of a primary TNBC tumor can 'prime' the lung microenvironment in preparation for metastasis.

PLK4 as a potential target to enhance radiosensitivity in triple-negative breast cancer.

Radioresistance is one of the barriers to developing more effective therapies against the most aggressive, triple-negative, breast cancer (TNBC) subtype. In our previous studies, we showed that inhibition of Polo-like Kinase 4 (PLK4) by a novel drug, CFI-400945 significantly enhances the anticancer effects of radiotherapy (RT) compared to single treatment alone. Here we further investigate the role of PLK4 in enhancing radiation effects in TNBC and explore mechanisms of PLK4 inhibition and radiation combinatorial antiproliferative effects.

Importance of Incorporating the Perspectives of People with Cancer into Oncology Education: A Scoping Review.

Background: With the shift towards person-centered care (PCC) in oncology, there is a need for parallel evolution of oncology education programs to prepare the next generation of health professionals to deliver effective PCC. These programs should be designed utilizing perspectives from individuals who have lived experience with cancer to ensure that changes to education curricula translate to improved PCC in the clinic.

Objectives: Our goal was to identify existing literature describing such programs as well as identify gaps for further development.

Detection of Circulating Tumor DNA After Stereotactic Ablative Radiotherapy in Patients With Unbiopsied Lung Tumors (SABR-DETECT).

For patients with stage I/IIA non-small-cell lung cancer (NSCLC), surgical resection is the standard treatment. However, some of these patients are not candidates for surgery or refuse a surgical option. Definitive stereotactic ablative radiotherapy (SABR) is a standard approach in these patients.

Involvement of the AKT Pathway in Resistance to Erlotinib and Cabozantinib in Triple-Negative Breast Cancer Cell Lines.

Resistance to protein tyrosine kinase inhibitors (TKIs) presents a significant challenge in therapeutic target development for cancers such as triple-negative breast cancer (TNBC), where conventional therapies are ineffective at combatting systemic disease. Due to increased expression, the receptor tyrosine kinases EGFR (epidermal growth factor receptor) and c-Met are potential targets for treatment. However, targeted anti-EGFR and anti-c-Met therapies have faced mixed results in clinical trials due to acquired resistance.

Influence of Extracellular Vesicles on Lung Stromal Cells during Breast Cancer Metastasis.

Breast cancer is a prominent cause of cancer diagnosis and death in women globally, with over 90% of deaths being attributed to complications that arise from metastasis. One of the common locations for breast cancer metastasis is the lung, which is associated with significant morbidity and mortality. Curative treatments for metastatic breast cancer patients are not available and the molecular mechanisms that underlie lung metastasis are not fully understood.

Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial.

Background: Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy.

Methods: We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant).

Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells.

The lung is one of the deadliest sites of breast cancer metastasis, particularly for triple negative breast cancer (TNBC). We have previously shown that the lung produces several soluble factors that may enhance the metastatic behavior of TNBC, including E-, L-, and P-selectin. In this paper, we hypothesize that lung-derived selectins promote TNBC metastatic behavior and may serve as a potential therapeutic target.

EMT-independent detection of circulating tumor cells in human blood samples and pre-clinical mouse models of metastasis.

Circulating tumor cells (CTCs) present an opportunity to detect/monitor metastasis throughout disease progression. The CellSearch® is currently the only FDA-approved technology for CTC detection in patients. The main limitation of this system is its reliance on epithelial markers for CTC isolation/enumeration, which reduces its ability to detect more aggressive mesenchymal CTCs that are generated during metastasis via epithelial-to-mesenchymal transition (EMT).

Role of the Microenvironment in Regulating Normal and Cancer Stem Cell Activity: Implications for Breast Cancer Progression and Therapy Response.

The epithelial cells in an adult woman's breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment.

Molecular Mechanisms of Breast Cancer Metastasis to the Lung: Clinical and Experimental Perspectives.

Breast cancer is the most commonly diagnosed cancer in women worldwide, and >90% of breast cancer-related deaths are associated with metastasis. Breast cancer spreads preferentially to the lung, brain, bone and liver; termed organ tropism. Current treatment methods for metastatic breast cancer have been ineffective, compounded by the lack of early prognostic/predictive methods to determine which organs are most susceptible to developing metastases.

A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration-resistant Prostate Cancer: Canadian Cancer Trials Group Study IND205.

Background: In PTEN-loss models, the phosphatidylinositol 3-kinase (PI3K)/AKT and androgen receptor signaling pathways cross-regulate by reciprocal feedback whereby inhibition of one activates the other, creating a rationale for co-targeting. We studied the irreversible, pan-isoform inhibitor of Class I PI-3K PX-866 singly (part A) and with abiraterone acetate (AA) in patients on AA with rising prostate-specific antigen (PSA) (part B).

Patients And Methods: The primary endpoint was lack of progression at 12 weeks.

Magnetically Guided Self-Assembled Protein Micelles for Enhanced Delivery of Dasatinib to Human Triple-Negative Breast Cancer Cells.

Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid-coated magnetite (FeO) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles.

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer.

Importance: A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need.

Objective: To determine whether a validated assay for the nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells can determine differential overall survival among patients with mCRPC treated with taxanes vs ARS inhibitors.

Design, Setting, And Participants: This blinded correlative study conducted from December 31, 2012, to September 1, 2016, included 142 patients with histologically confirmed mCRPC and who were treated at Memorial Sloan Kettering Cancer Center, The Royal Marsden, or the London Health Sciences Centre.

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis.

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging.