Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development.

TOWARDS Study: Patient-Derived Xenograft Engraftment Predicts Poor Survival in Patients With Newly Diagnosed Triple-Negative Breast Cancer.

Purpose: Assessing risk of recurrence for nonmetastatic triple-negative breast cancer (TNBC) is a key determinant of therapeutic strategy. The best predictor of recurrence risk is failure to achieve a pathologic complete response after preoperative chemotherapy, but it imperfectly correlates with the definitive end points of relapse-free and overall survival (OS). The inability to accurately predict recurrence has led to increasingly toxic treatment regimens for patients with early-stage TNBC.

MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes.

Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

Purpose: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV).

Methods: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium.

D-TERMINED, a phase 1 trial in newly diagnosed high-grade glioma with temozolomide, radiation, and minocycline followed by adjuvant minocycline/temozolomide.

Background: Standard treatment for newly diagnosed high-grade gliomas remains suboptimal. Preclinical data indicate that mesenchymal transition and radiation resistance in glioblastoma are driven by NF-κB and microglia activation, which can be inhibited by minocycline. We assessed the safety and efficacy of minocycline combined with standard radiation and temozolomide in newly diagnosed high-grade gliomas.

Moderating influences on parents' fatalistic beliefs about cancer and their association with sun safety behaviors among children of melanoma survivors: Implications for treatment.

The purpose of this study is to examine the association between parents' fatalism about melanoma and their children's sun protection, and the potential moderating role of parent-child communication. In this observational study of = 69 melanoma-surviving parents of children ages 8-17, parents reported on their own melanoma fatalism, as well as their children's sun safety behaviors and parent-child discussion about sun safety. Parent gender, family history of melanoma, and frequency of parent-child discussions moderated the relationship between parents' fatalism and children's sun safety behaviors.

ARF6-dependent endocytic trafficking of the Interferon-γ receptor drives adaptive immune resistance in cancer.

Adaptive immune resistance (AIR) is a protective process used by cancer to escape elimination by CD8 T cells. Inhibition of immune checkpoints PD-1 and CTLA-4 specifically target Interferon-gamma (IFNγ)-driven AIR. AIR begins at the plasma membrane where tumor cell-intrinsic cytokine signaling is initiated.

The Family Lifestyles, Actions and Risk Education (FLARE) study: Protocol for a randomized controlled trial of a sun protection intervention for children of melanoma survivors.

Background: Children of parents who had melanoma are more likely to develop skin cancer themselves owing to shared familial risks. The prevention of sunburns and promotion of sun-protective behaviors are essential to control cancer among these children. The Family Lifestyles, Actions and Risk Education (FLARE) intervention will be delivered as part of a randomized controlled trial to support parent-child collaboration to improve sun safety outcomes among children of melanoma survivors.

Electrical Impedance Dermography Differentiates Squamous Cell Carcinoma In Situ from Inflamed Seborrheic Keratoses.

There are no currently available low-cost, noninvasive methods for discerning the depth of squamous cell carcinoma (SCC) invasion or distinguishing SCC from its benign mimics, such as inflamed seborrheic keratosis (SK). We studied 35 subjects with subsequently confirmed SCC or SK. Subjects underwent electrical impedance dermography measurements at six frequencies to assess the electrical properties of the lesion.

Three pathologic criteria for reproducible diagnosis of colonic sessile serrated lesion versus hyperplastic polyp.

Colonic SSLs are thought to predispose to ∼30% of colonic adenocarcinomas. This increased risk, compared to benign HPs, makes their distinction vitally important. However, no gold standard exists to differentiate them, and wide observer variability is reported.

Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma.

The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients' plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach.

Associations of combined physical activity and body mass index groups with colorectal cancer survival outcomes.

Background: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes.

Methods: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk).

Phase I Trial of Combination Therapy With Avelumab and Cabozantinib in Patients With Newly Diagnosed Metastatic Clear Cell Renal Cell Carcinoma.

Background: Combination immunotherapy is now considered the standard first-line therapy for patients with metastatic clear cell renal cell carcinoma (mccRCC) after multiple clinical trials demonstrated improved overall survival compared with single-agent tyrosine kinase inhibitors. Cabozantinib modulates critical components of the immune system, such as decreasing regulatory T cells and increasing T-effector cell populations, and is approved for the treatment of mRCC. Avelumab is a human IgG1 monoclonal antibody that binds to programmed death-ligand 1 protein and inhibits the interaction with PD-1.

Prospective Pilot Study of F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

PET/CT with F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT.

Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma.

Purpose: We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC).

Materials And Methods: We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC).

A phase I open-label study of the safety and efficacy of apatinib (rivoceranib) administered to patients with advanced malignancies to improve sensitivity to pembrolizumab in the second- or later-line setting (APPEASE).

Objective: APPEASE is a phase I study to assess the safety, dosing, and efficacy of rivoceranib (a selective, small-molecule inhibitor of VEGFR2) in combination with pembrolizumab. We aimed to treat patients with metastatic malignancies who have progressed through at least first-line therapy, with pembrolizumab 200 mg every 3 weeks, as well as escalating doses of rivoceranib until disease progression or unacceptable toxicity.

Results: Five patients were enrolled on the starting dose of rivoceranib 300 mg once daily.

Improving Bone Health in Patients with Metastatic Prostate Cancer with the Use of Algorithm-Based Clinical Practice Tool.

Background: The bone health of patients with locally advanced and metastatic prostate cancer is at risk from treatment-related bone density loss and skeletal-related events from metastatic disease in bones. Evidence-based guidelines recommend using denosumab or zoledronic acid at bone metastasis-indicated dosages in the setting of castration-resistant prostate cancer with bone metastases and at the osteoporosis-indicated dosages in the hormone-sensitive setting in patients with a significant risk of fragility fracture. For the concerns of jaw osteonecrosis, a dental evaluation is recommended before starting bone-modifying agents.

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients.

Comprehensive evaluation and efficient classification of BRCA1 RING domain missense substitutions.

BRCA1 is a high-risk susceptibility gene for breast and ovarian cancer. Pathogenic protein-truncating variants are scattered across the open reading frame, but all known missense substitutions that are pathogenic because of missense dysfunction are located in either the amino-terminal RING domain or the carboxy-terminal BRCT domain. Heterodimerization of the BRCA1 and BARD1 RING domains is a molecularly defined obligate activity.

Masculinity Barriers to Ever Completing Colorectal Cancer Screening among American Indian/Alaska Native, Black, and White Men (Ages 45-75).

Disparities in colorectal cancer (CRC) mortality among White, Black, and American Indian/Alaska Native (AIAN) men are attributable to differences in early detection screening. Determining how masculinity barriers influence CRC screening completion is critical for cancer prevention and control. To determine whether masculinity barriers to medical care are associated with lower rates of ever completing CRC screening, a survey-based study was employed from December 2020-January 2021 among 435 White, Black, and AIAN men (aged 45-75) who resided in the US.

A Randomized Double-blind Placebo-controlled Trial of Oral Aspirin for Protection of Melanocytic Nevi Against UV-induced DNA Damage.

DNA damage plays a role in ultraviolet (UV)-induced melanoma. We previously showed that aspirin (ASA) can suppress prostaglandin-E (PGE) and protect melanocytes from UV-induced DNA damage in mice, and suggested that taking ASA before acute sun exposure may reduce melanoma risk. We conducted a prospective randomized placebo-controlled trial to determine if orally administered ASA could suppress PGE in plasma and nevi and protect nevi from UV-induced DNA damage.

Radium-223 plus Enzalutamide Versus Enzalutamide in Metastatic Castration-Refractory Prostate Cancer: Final Safety and Efficacy Results.

Lessons Learned: Long-term safety of radium-223 with enzalutamide was confirmed in this clinical trial. PSA-PFS2 was prolonged with the combination compared with enzalutamide alone.

Background: Previously, we showed the combination of radium-223 and enzalutamide to be safe and associated with improved efficacy based on a concomitant decline in serum bone metabolism markers compared with enzalutamide alone in a phase II trial of men with metastatic castration-resistant prostate cancer (mCRPC) [1].

Correlation between FDG-PET uptake and survival in patients with primary brain tumors.

This study evaluates F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) semi-quantitative analysis as biomarker of tumor aggressiveness and predictor of survival in patients with primary brain tumors. Semi-quantitative analyses (SUVmax, SUVmean) were derived from FDG PET images in 78 patients with suspected recurrence of primary brain tumors based on MRI. SUVmax and the ratio of lesion SUVmax to the SUVmean of contralateral white matter (SUVmax/WM) were measured.

A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker.

Background: Disulfiram and metals inactivate key oncoproteins resulting in anti-neoplastic activity. The goal of this study was to determine the maximum tolerated dose of copper when administered with disulfiram in patients with advanced solid tumors and liver involvement.

Methods: Disulfiram 250 mg was administered daily in 28-day cycles.