Development of a novel malignant colorectal polyp prognostic nomogram.

Background: There is uncertainty when determining the optimal treatment for malignant polyps. Clinicians must balance the oncological risk of a malignant polyp with the risk of morbidity and mortality from surgery. This study developed an online risk-calculator using machine-learning techniques to predict the risk of an adverse outcome from a malignant colorectal polyp following polypectomy.

Antigen presentation potential is variable among human ovarian tumour and syngeneic murine models and dictates pre-clinical outcomes of immunotherapy.

High grade serous ovarian carcinoma (HGSC) is a fatal gynaecological malignancy with limited therapeutic options. Immunotherapies targeting MHC-I-dependent antigen presentation offer potential. Currently, the antigen presentation machinery (APM) of widely used syngeneic murine HGSC models remains poorly characterised, limiting translational relevance.

Highlights of 2024. Broadening anti-cancer immunotherapy modalities with antibody-drug conjugates: emerging insights from clinical studies.

In this article for the "Highlights of 2024" series, we discuss antibody-drug conjugates (ADCs), which are an emerging class of targeted cancer therapies that harness the specificity of monoclonal antibodies to deliver cytotoxic agents directly to tumor cells. ADCs bind to tumor-associated antigens, undergo internalization via receptor-mediated endocytosis, and release their cytotoxic payload intracellularly, reducing systemic toxicity. This highly selective mechanism has led to significant advancements in oncology, improving treatment efficacy while minimizing adverse effects.

Receptor CDCP1 Is a Potential Target for Personalized Imaging and Treatment of Poor Outcome HER2+, Triple-Negative, and Metastatic ER+/HER2- Breast Cancers.

Purpose: Receptor CUB domain-containing protein 1 (CDCP1) was evaluated as a target for detection and treatment of breast cancer.

Experimental Design: CDCP1 expression was assessed immunohistochemically in tumors from 423 patients [119 triple-negative breast cancer (TNBC); 75 HER2+; and 229 ER+/HER2-, including 228 primary tumors and 229 lymph node and 47 distant metastases). Cell cytotoxicity induced in vitro by a CDCP1-targeting antibody-drug conjugate (ADC), consisting of the human/mouse chimeric antibody ch10D7 and the microtubule disruptor monomethyl auristatin E (MMAE), was quantified, including in combination with HER-targeting ADC trastuzumab emtansine (T-DM1).

Aurora B inhibition induces hyper-polyploidy and loss of long-term proliferative potential in RB and p53 defective cells.

Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo.

Aurora B inhibitors promote RB hypophosphorylation and senescence independent of p53-dependent CDK2/4 inhibition.

Aurora B kinase (AURKB) inhibitors have been trialled in a range of different tumour types but are not approved for any indication. Expression of the human papilloma virus (HPV) oncogenes and loss of retinoblastoma (RB) protein function has been reported to increase sensitivity to AURKB inhibitors but the mechanism of their contribution to sensitivity is poorly understood. Two commonly reported outcomes of AURKB inhibition are polyploidy and senescence, although their relationship is unclear.

Identification and characterization of TM4SF1 tumor self-seeded cells.

Tumor self-seeding is a process whereby circulating tumor cells (CTCs) recolonize the primary tumor, which promotes tumor growth, angiogenesis, and invasion. However, the detailed nature and functions of tumor self-seeded cells (TSCs) have not been well defined due to challenges in tracking and isolating TSCs. Here, we report an accurate animal model using photoconvertible tagging to recapitulate the spontaneous process of tumor self-seeding and identify TSCs as a subpopulation of primary tumor cells with enhanced invasiveness and survival.

Estimation of risk posed by malignant polyps amongst colorectal surgeons in Australia and New Zealand.

Purpose: The estimation of the risk posed by malignant polyps for residual or lymphatic disease plays a central role. This study investigated colorectal surgeons' assessment of these risks associated with malignant polyps.

Methods: A cross-sectional questionnaire was electronically administered to colorectal surgeons in Australia and New Zealand in October 2022.

Inhibition of Aurora B kinase (AURKB) enhances the effectiveness of 5-fluorouracil chemotherapy against colorectal cancer cells.

Background: 5-Fluorouracil (5-FU) remains a core component of systemic therapy for colorectal cancer (CRC). However, response rates remain low, and development of therapy resistance is a primary issue. Combinatorial strategies employing a second agent to augment the therapeutic effect of chemotherapy is predicted to reduce the incidence of treatment resistance and increase the durability of response to therapy.

UGDH promotes tumor-initiating cells and a fibroinflammatory tumor microenvironment in ovarian cancer.

Background: Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that are supported by a complex extracellular matrix and immunosuppressive microenvironment. To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen.

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.

Background & Aims: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action.

Methods: Muc13 and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin.

Discovery and validation of serum glycoprotein biomarkers for high grade serous ovarian cancer.

Purpose: This study aimed to identify serum glycoprotein biomarkers for early detection of high-grade serous ovarian cancer (HGSOC), the most common and aggressive histotype of ovarian cancer.

Experimental Design: The glycoproteomics pipeline lectin magnetic bead array (LeMBA)-mass spectrometry (MS) was used in age-matched case-control serum samples. Clinical samples collected at diagnosis were divided into discovery (n = 30) and validation (n = 98) sets.

Reactive Oxygen Species as Mediators of Disease Progression and Therapeutic Response in Colorectal Cancer.

Reactive oxygen species (ROS) are critical to normal cellular function with redox homeostasis achieved by balancing ROS production with removal through detoxification mechanisms. Many of the conventional chemotherapies used to treat colorectal cancer (CRC) derive a proportion of their cytotoxicity from ROS generation, and resistance to chemotherapy is associated with elevated detoxification mechanisms. Furthermore, cancer stem cells demonstrate elevated detoxification mechanisms making definitive treatment with existing chemotherapy challenging.

Malignant polyps in the COVID-19 era: a population-based analysis.

Background: Malignant polyps represent the early development of colorectal adenocarcinoma. During 2020, there was widescale rationing of health-care resources in response to the COVID-19 pandemic. In particular there was deferral of some colonoscopy procedures required for timely malignant polyp detection.

Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.

Approximately 50%-55% of high-grade serous ovarian carcinoma (HGSOC) patients have MYC oncogenic pathway activation. Because MYC is not directly targetable, we have analyzed molecular pathways enriched in MYC-high HGSOC tumors to identify potential therapeutic targets. Here, we report that MYC-high HGSOC tumors show enrichment in genes controlled by NRF2, an antioxidant signaling pathway, along with increased thioredoxin redox activity.

CBL0137 impairs homologous recombination repair and sensitizes high-grade serous ovarian carcinoma to PARP inhibitors.

Background: High-grade serous ovarian carcinomas (HGSCs) are a heterogeneous subtype of epithelial ovarian cancers and include serous cancers arising in the fallopian tube and peritoneum. These cancers are now subdivided into homologous recombination repair (HR)-deficient and proficient subgroups as this classification impacts on management and prognosis. PARP inhibitors (PARPi) have shown significant clinical efficacy, particularly as maintenance therapy following response to platinum-based chemotherapy in BRCA-mutant or homologous recombination (HR)-deficient HGSCs in both the 1st and 2nd line settings.

CUB Domain-Containing Protein 1 (CDCP1) is a rational target for the development of imaging tracers and antibody-drug conjugates for cancer detection and therapy.

An antibody-drug conjugate (ADC) is a targeted therapy consisting of a cytotoxic payload that is linked to an antibody which targets a protein enriched on malignant cells. Multiple ADCs are currently used clinically as anti-cancer agents significantly improving patient survival. Herein, we evaluated the rationale of targeting the cell surface oncoreceptor CUB domain-containing protein 1 (CDCP1) using ADCs and assessed the efficacy of CDCP1-directed ADCs against a range of malignant tumors.

In comparison with polypectomy, colorectal resection is associated with improved survival for patients diagnosed with malignant polyps.

Aim: Patients diagnosed with a malignant polyp generally have favourable overall survival (OS) and cancer-specific survival (CSS). However, it is unclear how choice in management for malignant polyps may affect survival.

Methods: Data from the Queensland Oncology Repository was analysed to derive a population wide assessment of the impact of management strategy on OS and CSS for patients diagnosed with malignant polyps.

Timing of surveillance colonoscopy following malignant colorectal polypectomy in Queensland.

Introduction: The management of malignant polyps presents a treatment challenge between a colorectal resection and polypectomy alone. Patients managed with polypectomy alone typically undergo surveillance for recurrent or metastatic disease, however, optimal timing of surveillance methods remains unclear. Guidelines recommend for completely resected malignant polyps, that a surveillance colonoscopy be perform 12 months from diagnosis.

Missing parameters in malignant polyp histology reports: can appropriate decisions be made?

The treatment of colorectal malignant polyps is dependent upon quality reporting of the histopathological features known to predict the risk of residual disease or lymph node metastasis. The Royal College of Pathologists of Australasia (RCPA) has produced protocols covering mandatory and recommended pathological parameters to be included in the pathology reporting of malignant polyps. This paper aimed to assess the quality of the pathological reporting in a population-wide analysis from 2011-2019 in Queensland, Australia.

Management of high and low risk malignant polyps: a population-wide analysis.

Aim: The management of malignant polyps is a treatment dilemma in selecting between polypectomy and colorectal resection. To assist clinicians, guidelines have been developed by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to provide treatment recommendations.

Methods: This study compared management strategy based on the ACPGBI risk categorization for malignant polyps.

A population-based study of the management of rectal malignant polyps and the use of trans-anal surgery.

Introduction: Rectal malignant polyps can be managed by use of trans-anal resections (TAR). Traditional techniques of resection have been replaced by use of platforms such as trans-anal minimally invasive surgery (TAMIS) or trans-anal endoscopic microsurgery (TEM). This study reviewed the management of rectal malignant polyps, in particular focussing on when clinicians used TAR.

Correction: Alpha-Tomatine Attenuation of In Vivo Growth of Subcutaneous and Orthotopic Xenograft Tumors of Human Prostate Carcinoma PC-3 Cells Is Accompanied by Inactivation of Nuclear Factor-Kappa B Signaling.

[This corrects the article DOI: 10.1371/journal.pone.