Project description:Liver metastases are the most common site of metastatic spread in colorectal cancer. Current treatment approaches involve effective systemic therapies in combination with surgical and/or interventional strategies. Multimodal strategies greatly improved clinical outcomes of patients with metastatic colorectal cancer over the last decades. Identification of predictive and prognostic biomarkers helped to comprehensively refine individual targeted treatment approaches and resulted in median overall survival rates of 30 months or longer. Current guidelines, thus, recommend treatment selection according to patients' performance status, tumor localization and stage as well as the tumor's molecular and genetic status. Here, we outline the latest developments in molecular decision-making for patients with upfront resectable, potentially or initially unresectable and non/never-resectable colorectal cancer liver metastases.
Project description:Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase III studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/PD-L1 showed durable efficacy in phase I studies, and phase III evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase II study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.
Project description:Colorectal cancer is the second most common malignancy diagnosed in Canada. Despite declining incidence and mortality rates in recent years, there is still a significant number of cases that are metastatic at presentation. Fluoropyrimidine-based chemotherapy was the backbone of colorectal cancer treatment, but the addition of irinotecan and oxaliplatin to form combination regimens has significantly improved overall survival. In the past decade, the development of novel biologic agents including therapies directed against vascular endothelial growth factor and epidermal growth factor receptor has further altered the landscape of metastatic colorectal cancer treatment. However, clinical trials have demonstrated that not all patients respond to these therapies similarly and consideration must be given to individual patient- and tumor-related factors. A more tailored and biomarker driven approach to treatment selection can optimize outcomes and avoid unnecessary adverse effects. In this review article, we offer a comprehensive overview of the panel of clinical- and tumor-associated characteristics that influence treatment decisions in metastatic colorectal cancer and how this sets the foundation for a more personalized treatment strategy in oncology.
Project description:BACKGROUND: Breast cancer follow-up is not tailored to the risk of locoregional recurrences (LRRs) in individual patients or as a function of time. The objective of this study was to identify prognostic factors and to estimate individual and time-dependent LRR risk rates. METHODS: Prognostic factors for LRR were identified by a scoping literature review, expert consultation, and stepwise multivariate regression analysis based on 5 years of data from women diagnosed with breast cancer in the Netherlands in 2005 or 2006 (n=17,762). Inter-patient variability was elucidated by examples of 5-year risk profiles of average-, medium-, and high-risk patients, whereby 6-month interval risks were derived from regression estimates. RESULTS: Eight prognostic factors were identified: age, tumour size, multifocality, gradation, adjuvant chemo-, adjuvant radiation-, hormonal therapy, and triple-negative receptor status. Risk profiles of the low-, average-, and high-risk example patients showed non-uniform distribution of recurrence risks (2.9, 7.6, and 9.2%, respectively, over a 5-year period). CONCLUSION: Individual risk profiles differ substantially in subgroups of patients defined by prognostic factors for recurrence and over time as defined in 6-month time intervals. To tailor follow-up schedules and to optimise allocation of scarce resources, risk factors, frequency, and duration of follow-up should be taken into account.
Project description:BackgroundCurrent decision-making for the treatment of breast cancer liver metastases (BCLM) using ablation lacks strong evidence, especially for patients combined with extrahepatic metastases.PurposeTo assess whether ablation plus systemic therapy (AS) improves survival outcomes in patients with BCLM compared to systemic therapy alone.Materials and methodsThis retrospective study analyzed patients with BCLM who received either AS or systemic therapy alone. Propensity score matching (PSM) and survival analysis were performed, taking into account factors like the characteristics of primary breast cancer, liver metastases and systemic therapies received.ResultsThe study included 1021 female patients, with a median follow-up of 39.6 months. Of these patients, 132 underwent AS and 836 received systemic therapy alone. After PSM, among patients with BCLM (≤3 tumors, each ≤3 cm), the median overall survival (OS) for those treated with AS or systemic therapy alone was 65.5 and 40.4 months, respectively (HR = 0.48, p = .003); in the subset of patients with extrahepatic metastases, the median OS for those treated with AS and systemic therapy alone was 46.4 and 40.8 months, respectively (HR = 0.58, p = .047). Among patients with >3 cm or >3 lesions, the median OS for those treated with AS or systemic therapy alone was 45.2 and 29 months, respectively (HR = 0.67, p = .084).ConclusionsAmong patients with BCLM (≤3 tumors, each ≤3 cm), AS provide longer survival compared to systemic therapy alone, even with extrahepatic metastases. For patients with larger or more numerous metastases (>3 cm or >3 lesions), AS may provide survival benefit, but further validation is needed.
Project description:ABSTARCT:This work explores a new class of vortex/magnetite/iron oxide nanoparticles designed for magnetic hyperthermia applications. These nanoparticles, named Vortex Iron oxide Particles (VIPs), are an alternative to the traditional Superparamagnetic Iron Oxide Nanoparticles (SPIONs), since VIPs present superior heating power while fulfilling the main requirements for biomedical applications (low cytotoxicity and nonremanent state). In addition, the present work demonstrates that the synthesized VIPs also promote an internalization and aggregation of the particles inside the cell, resulting in a highly localized hyperthermia in the presence of an alternating magnetic field. Thereby, we demonstrate a new and efficient magnetic hyperthermia strategy in which a small, but well localized, concentration of VIPs can promote an intracellular hyperthermia process.
Project description:The tumor microenvironment (TME) is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded by the components of the extracellular matrix (ECM). Glycosaminoglycans (GAGs), natural biomacromolecules, essential ECM, and cell membrane components are extensively altered in cancer tissues. During disease progression, the GAG fine structure changes in a manner associated with disease evolution. Thus, changes in the GAG sulfation pattern are immediately correlated to malignant transformation. Their molecular weight, distribution, composition, and fine modifications, including sulfation, exhibit distinct alterations during cancer development. GAGs and GAG-based molecules, due to their unique properties, are suggested as promising effectors for anticancer therapy. Considering their participation in tumorigenesis, their utilization in drug development has been the focus of both industry and academic research efforts. These efforts have been developing in two main directions; (i) utilizing GAGs as targets of therapeutic strategies and (ii) employing GAGs specificity and excellent physicochemical properties for targeted delivery of cancer therapeutics. This review will comprehensively discuss recent developments and the broad potential of GAG utilization for cancer therapy.
Project description:Hepatic metastases are a major cause of morbidity and mortality for patients with cancer. Apart from curative resection, which offers patients the potential for long-term survival, an array of locoregional therapies, with limited evidence of improving survival, are used to treat them. The authors use examples from the realm of gastrointestinal cancer, largely focusing on the experience of patients with neuroendocrine cancer, hepatobiliary cancer, and colorectal cancer, to suggest that current systemic therapies offer, at minimum, similar survival outcomes for patients compared with these locoregional approaches.
Project description:Thyroid cancer is the most common endocrine malignancy. While surgery remains the mainstay of the treatment of all different histologies, for differentiated thyroid cancers, radioactive iodine also plays an important role in management. Once tumor becomes radio-iodine refractory, it needs systemic therapy. Earlier, these tumors had very dismal prognosis. However, with the advancement of technology and research, it has become clear now that thyroid cancer cells are driven by various mutations. Targeting these oncogenic drivers by various molecules have proven to be effective therapeutic strategy in thyroid cancer. Besides, as in other solid tumors, immunotherapy is also being evaluated in thyroid cancer. While these new therapeutic approaches have revolutionized the treatment on advanced/metastatic thyroid cancer, there are definite challenges which limit their use in common clinical practice. These challenges include higher treatment cost and lack of testing to identify the driver mutations. Moreover, there is still need for further research in thyroid cancers to identify oncogenic targets and agent to act upon them.
Project description:Gallbladder cancer is an aggressive cancer that continues to be an important health care issue in certain regions of the world such as Southeast Asia and Latin America. Most patients are diagnosed at an advanced, unresectable stage and systemic therapy is their only option. Gallbladder cancer patients have traditionally been included in clinical trials for biliary tract cancer. Thus, systemic chemotherapy options for this cancer are similar to those for cholangiocarcinoma, including gemcitabine and cisplatin in the first line and FOLFOX in the second-line setting. Ongoing phase III clinical trials may change the systemic therapy paradigm for this cancer. Molecular profiling has indicated important genetic differences between gallbladder cancer and cholangio-carcinoma, which affects choice of targeted therapy. Her2/neu amplification, PIK3CA mutations and DNA repair genetic aberrations are relatively frequent and represent actionable targets for this cancer.