59,727 results match your criteria Targeted Cancer Therapy


Systemic treatment of advanced hepatocellular cancer: new hope on the horizon.

Expert Rev Anticancer Ther 2019 Feb 22. Epub 2019 Feb 22.

a Olivia Newton-John Cancer Wellness and Research Centre , 145 Studley Road, Heidelberg , VIC 3084 , Australia.

Introduction: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality in the world. The majority of the patients present at an advanced or incurable stage where neither locoregional treatment nor combination treatment of locoregional treatment and systemic therapies are feasible. For decades sorafenib was the only treatment option available for advanced HCC. Read More

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http://dx.doi.org/10.1080/14737140.2019.1585245DOI Listing
February 2019

Choosing the right pharmacotherapy for non-Hodgkin's lymphoma: does one size fit all?

Expert Opin Pharmacother 2019 Feb 22:1-3. Epub 2019 Feb 22.

a Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA.

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http://dx.doi.org/10.1080/14656566.2019.1582643DOI Listing
February 2019

Magnolol induces cell death through PI3K/Akt-mediated epigenetic modifications boosting treatment of BRAF- and NRAS-mutant melanoma.

Cancer Med 2019 Feb 21. Epub 2019 Feb 21.

Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.

Most BRAF-mutant melanoma patients experience a fulminate relapse after several months of treatment with BRAF/MEK inhibitors. To improve therapeutic efficacy, natural plant-derived compounds might be considered as potent additives. Here, we show that magnolol, a constituent of Magnolia officinalis, induced G1 arrest, apoptosis and cell death in BRAF- and NRAS-mutant melanoma cells at low concentration, with no effect in BRAF- and NRAS wild-type melanoma cells and human keratinocytes. Read More

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http://dx.doi.org/10.1002/cam4.1978DOI Listing
February 2019

uMUC1-Targeting Magnetic Resonance Imaging of Therapeutic Response in an Orthotropic Mouse Model of Colon Cancer.

Mol Imaging Biol 2019 Feb 21. Epub 2019 Feb 21.

Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, 775 Woodlot Dr., Rm. 3.111, East Lansing, MI, 48823, USA.

Purpose: Noninvasive assessment of chemotherapeutic response in colon cancer would tremendously aid in therapeutic intervention of cancer patients and improve outcomes. The aim of the study was to evaluate the feasibility of a noninvasive assessment of chemotherapeutic response by magnetic resonance imaging utilizing underglycosylated mucin 1 (uMUC1) tumor antigen as a biomarker of therapeutic response in a colon cancer mouse model.

Procedures: The study was performed by applying molecular imaging approach based on targeting uMUC1 with specific dual-modality imaging probe (MN-EPPT). Read More

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http://dx.doi.org/10.1007/s11307-019-01326-5DOI Listing
February 2019

Implementing TMB measurement in clinical practice: considerations on assay requirements.

ESMO Open 2019 24;4(1):e000442. Epub 2019 Jan 24.

Department of Biopathology, Centre Jean Perrin, Clermont-Ferrand, France.

Clinical evidence demonstrates that treatment with immune checkpoint inhibitor immunotherapy agents can have considerable benefit across multiple tumours. However, there is a need for the development of predictive biomarkers that identify patients who are most likely to respond to immunotherapy. Comprehensive characterisation of tumours using genomic, transcriptomic, and proteomic approaches continues to lead the way in advancing precision medicine. Read More

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http://dx.doi.org/10.1136/esmoopen-2018-000442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350758PMC
January 2019

Access to high-cost drugs for advanced breast cancer in Latin America, particularly trastuzumab.

Ecancermedicalscience 2019 22;13:898. Epub 2019 Jan 22.

Latin American Cooperative Oncology Group, 99 A, Av Ipiranga 6681, Porto Alegre, RS 90619-900, Brazil.

Provision of high-level healthcare is a challenge for all low- to middle-income countries (LMICs) since healthcare systems are heterogeneous, face many challenges such as inadequate funding, inequitable distribution of resources and services and usually are not adequately equipped to deal with a huge problem such as breast cancer. The development of anti-HER2 therapies can be considered one of the most important examples of the translation of molecular biology knowledge into clinical benefits for cancer patients. While a variety of novel therapeutic strategies are emerging, current treatment regimens remain focussed on targeted therapy with monoclonal antibodies, mainly trastuzumab, the first agent developed in this field. Read More

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http://dx.doi.org/10.3332/ecancer.2019.898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372298PMC
January 2019

Precision medicine for locally advanced breast cancer: frontiers and challenges in Latin America.

Ecancermedicalscience 2019 22;13:896. Epub 2019 Jan 22.

Departamento de Medicina Oncológica, Oncosalud-AUNA, Lima 15036, Perú.

Advances in high-throughput technologies and their involvement in the 'omics' of cancer have made possible the identification of hundreds of biomarkers and the development of predictive and prognostic platforms that model the management of cancer from evidence-based medicine to precision medicine. Latin America (LATAM) is a region characterised by fragmented healthcare, high rates of poverty and disparities to access to a basic standard of care not only for cancer but also for other complex diseases. Patients from the public setting cannot afford targeted therapy, the facilities offering genomic platforms are scarce and the use of high-precision radiotherapy is limited to few facilities. Read More

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http://dx.doi.org/10.3332/ecancer.2019.896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372295PMC
January 2019

Perspectives on immunotherapy via oncolytic viruses.

Infect Agent Cancer 2019 11;14. Epub 2019 Feb 11.

Department of Molecular Medicine, University of Padua, Via A. Gabelli, 63, 35121 Padua, Italy.

Background: With few exceptions, current chemotherapy and radiotherapy protocols only obtain a slightly prolonged survival with severe adverse effects in patients with advanced solid tumors. In particular, most solid malignancies not amenable to radical surgery still carry a dismal prognosis, which unfortunately is also the case for relapsing disease after surgery. Even though targeted therapies obtained good results, clinical experience showed that tumors eventually develop resistance. Read More

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http://dx.doi.org/10.1186/s13027-018-0218-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371415PMC
February 2019

Beyond KRAS: Practical Molecular Targets in Pancreatic Adenocarcinoma.

Case Rep Oncol 2019 Jan-Apr;12(1):7-13. Epub 2019 Jan 4.

Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Pancreatic adenocarcinoma (PDAC) has a grim prognosis. Molecular and genomic analyses revealed that the striking majority of these tumors are driven by KRAS mutation, currently not amenable to targeted therapy. However, other driver mutations were found in a small fraction of patients. Read More

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http://dx.doi.org/10.1159/000496018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381925PMC
January 2019

Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates.

Sci Rep 2019 Feb 21;9(1):2443. Epub 2019 Feb 21.

Cancer Immunology Discovery, Oncology Research and Development, Worldwide Research and Development, Pfizer Inc., 230 E Grand Ave, South San Francisco, CA, 94080, USA.

Antibody-drug conjugates (ADCs) are promising therapies for haematological cancers. Historically, their therapeutic benefit is due to ADC targeting of lineage-restricted antigens. The C-X-C motif chemokine receptor 4 (CXCR4) is attractive for targeted therapy of haematological cancers, given its expression in multiple tumour types and role in cancer "homing" to bone marrow. Read More

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http://dx.doi.org/10.1038/s41598-019-38745-xDOI Listing
February 2019

K-Ras G-domain binding with signaling lipid Phosphatidyl inositol (4,5) phosphate (PIP2): Membrane association, protein orientation and function.

J Biol Chem 2019 Feb 21. Epub 2019 Feb 21.

Physiology and Biophysics, Case Western Reserve Univ. Medical School, United States.

Ras genes potently drive human cancers, with mutated proto-oncogene GTPase KRAS4B (K-Ras4B) being the most abundant isoform. Targeted inhibition of oncogenic gene products is considered the "holy grail" of present-day cancer therapy, and recent discoveries of small-molecule KRas4B inhibitors were made thanks to a deeper understanding of the structure and dynamics of this GTPase. Since interactions with biological membranes are key for Ras function, Ras-lipid interactions have become a major focus, especially since such interactions evidently involve both the Ras C terminus for lipid anchoring and its G-protein domain. Read More

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http://dx.doi.org/10.1074/jbc.RA118.004021DOI Listing
February 2019

CD20 and CD37 antibodies synergize to activate complement by Fc-mediated clustering.

Haematologica 2019 Feb 21. Epub 2019 Feb 21.

University of Virginia School of Medicine, Charlottesville, Virginia, USA.

CD20 monoclonal antibody therapies have significantly improved the outlook for patients with B-cell malignancies. However many patients acquire resistance, demonstrating the need for new and improved drugs. We previously demonstrated that the natural process of antibody hexamer formation on targeted cells allows for optimal induction of complement-dependent cytotoxicity. Read More

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http://dx.doi.org/10.3324/haematol.2018.207266DOI Listing
February 2019

miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC.

Biochem Biophys Res Commun 2019 Feb 18. Epub 2019 Feb 18.

Department of Oncology-Pathology, Visionsgatan 4, Karolinska Institutet, S-17164, Stockholm, Sweden; Theme Cancer, Karolinska University Hospital, S-17176, Stockholm, Sweden. Electronic address:

Lung cancer causes the highest number of cancer-related deaths worldwide. Resistance to therapy is a major clinical issue contributing to the poor prognosis of lung cancer. In recent years, targeted therapy has become a concept where subgroups of non-small cell lung cancer (NSCLC) with genetically altered receptor tyrosine kinases are targeted by tyrosine kinase inhibitors (TKIs). Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.02.016DOI Listing
February 2019

Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma.

J Immunother Cancer 2019 Feb 21;7(1):52. Epub 2019 Feb 21.

Department of Internal Medicine, Division of Medical Oncology, Basel, Switzerland.

Background: Treatment with a combination of PD-1 and CTLA-4 targeted checkpoint inhibition has improved outcome of melanoma patients and led to durable remissions but is also associated with significant toxicities. Endocrinopathies such as thyroiditis and hypophysitis are often seen, but other, rarer disturbances have also been described. Endocrinopathies affecting the parathyroid gland are rarely reported and no clear pathomechanism has been proposed. Read More

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http://dx.doi.org/10.1186/s40425-019-0528-xDOI Listing
February 2019

A good response of refractory mantel cell lymphoma to haploidentical CAR T cell therapy after failure of autologous CAR T cell therapy.

J Immunother Cancer 2019 Feb 21;7(1):51. Epub 2019 Feb 21.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: The aggressive form of Mantle cell non-hodgkin B cell lymphoma (MCL) has a dismal prognosis. Dual targeting BTK and BCL2 with ibrutinib and venetoclax has improved outcomes in MCL patients who were predicted not to respond to conventional therapy, but it is unlikely to be curative. Chimeric antigen receptor-modified T (CAR T) cells exhibit very effective function in elimination of relapsed/refractory B-cell lymphoid malignancies, we investigated their use in a patient with relapsed MCL. Read More

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http://dx.doi.org/10.1186/s40425-019-0529-9DOI Listing
February 2019

AMP-activated protein kinase: a potential therapeutic target for triple-negative breast cancer.

Breast Cancer Res 2019 Feb 21;21(1):29. Epub 2019 Feb 21.

Division of Cancer Research and Training, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, David Geffen UCLA School of Medicine, and UCLA Jonsson Comprehensive Cancer Center, 1748 E. 118th Street, Los Angeles, CA, 90059, USA.

Triple-negative breast cancer (TNBC) is an aggressive subset of breast carcinomas that lack expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Unlike other breast cancer subtypes, targeted therapy is presently unavailable for patients with TNBC. In spite of initial responses to chemotherapy, drug resistance tends to develop rapidly and the prognosis of metastatic TNBC is poor. Read More

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http://dx.doi.org/10.1186/s13058-019-1107-2DOI Listing
February 2019

Proteome profiling of triple negative breast cancer cells overexpressing NOD1 and NOD2 receptors unveils molecular signatures of malignant cell proliferation.

BMC Genomics 2019 Feb 21;20(1):152. Epub 2019 Feb 21.

SBP Medical Discovery Institute, 10901 North Torrey Pines Rd, La Jolla, CA, 92037, USA.

Background: Triple negative breast cancer (TNBC) is a malignancy with very poor prognosis, due to its aggressive clinical characteristics and lack of response to receptor-targeted drug therapy. In TNBC, immune-related pathways are typically upregulated and may be associated with a better prognosis of the disease, encouraging the pursuit for immunotherapeutic options. A number of immune-related molecules have already been associated to the onset and progression of breast cancer, including NOD1 and NOD2, innate immune receptors of bacterial-derived components which activate pro-inflammatory and survival pathways. Read More

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http://dx.doi.org/10.1186/s12864-019-5523-6DOI Listing
February 2019

The diagnostic accuracy of circulating free DNA for the detection of KRAS mutation status in colorectal cancer: A meta-analysis.

Cancer Med 2019 Feb 21. Epub 2019 Feb 21.

Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Shandong Province, Jinan, P.R. China.

KRAS mutations have been reported as a reliable biomarker for epidermal growth factor receptor (EGFR) targeted therapy and are also associated with poor prognosis in colorectal cancer (CRC) patients. However, limitations of detecting KRAS mutations in tissues are obvious. KRAS mutations in the peripheral blood can be detected as an alternative to tissue analysis. Read More

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http://dx.doi.org/10.1002/cam4.1989DOI Listing
February 2019

Recent advances in the development of Mcl-1 inhibitors for cancer therapy.

Pharmacol Ther 2019 Feb 18. Epub 2019 Feb 18.

Oncology, IMED Biotech Unit, AstraZeneca Boston. Electronic address:

Dysregulation of the mitochondrial apoptotic pathway controlled by members of the Bcl-2 protein family plays a central role in cancer development and resistance to conventional cytotoxic as well as targeted therapies. Hence, selective inhibition of pro-survival Bcl-2 family of proteins to activate apoptosis in malignant cells represents an exciting anti-cancer strategy. The remarkable clinical performance of the selective Bcl-2 antagonist venetoclax has highlighted the potential for selective inhibitors of the other pro-survival members of the Bcl-2 family, particularly Mcl-1. Read More

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http://dx.doi.org/10.1016/j.pharmthera.2019.02.007DOI Listing
February 2019

Aurora B kinase as a novel molecular target for inhibition the growth of osteosarcoma.

Mol Carcinog 2019 Feb 20. Epub 2019 Feb 20.

The Hormel Institute, University of Minnesota, 801 16th Ave NE, MN 55912, Austin, P.R. China.

Osteosarcoma is the primary human malignant tumor affecting bone. This cancer most frequently arises in children and adolescents, with a second peak in those over the age of 50. Currently, surgery followed by radiotherapy and chemotherapy are the main treatments, but long-term positive effects are very poor. Read More

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http://dx.doi.org/10.1002/mc.22993DOI Listing
February 2019

Inhibition of the hexosamine biosynthesis pathway potentiates cisplatin cytotoxicity by decreasing BiP expression in non-small cell lung cancer cells.

Mol Carcinog 2019 Feb 20. Epub 2019 Feb 20.

Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM 87108, US, China.

Platinum anticancer agents are essential components in chemotherapeutic regimens for non-small cell lung cancer (NSCLC) patients ineligible for targeted therapy. However, platinum-based regimens have reached a plateau of therapeutic efficacy; therefore, it is critical to implement novel approaches for improvement. The hexosamine biosynthesis pathway (HBP), which produces amino-sugar N-acetyl-glucosamine (GlcNAc) for protein glycosylation, is important for protein function and cell survival. Read More

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http://dx.doi.org/10.1002/mc.22992DOI Listing
February 2019

ALK Expression in Small Cell Lung Cancer.

Histopathology 2019 Feb 20. Epub 2019 Feb 20.

Dept of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.

Introduction: ALK immunohistochemistry has shifted from a screening tool to a sole determinant for ALK-targeted therapy. Recent articles have referred to SCLC transformation as a resistance mechanism after ALK inhibitor treatments, but few reports have addressed ALK expression in treatment-naïve SCLC in a comprehensive manner.

Methods: We examined ALK expression in a consecutive series of SCLC tumors, and the expression mechanism was analyzed regarding gene rearrangement, copy number changes, and point mutations. Read More

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http://dx.doi.org/10.1111/his.13842DOI Listing
February 2019

Dendron-polymer Conjugate based Crosslinked Micelles: A Robust and Versatile Nanosystem for Targeted Delivery.

Bioconjug Chem 2019 Feb 21. Epub 2019 Feb 21.

Among various nanomedicine platforms, biodegradable polymeric micelles offer a viable approach to targeted cancer therapy. Herein, we report fabrication of core-crosslinked micelles using dendron-polymer conjugates as building blocks. Hydrophobic polyester dendrons containing peripheral alkene groups are conjugated to a hydrophilic poly(ethylene glycol) based copolymer bearing activated ester groups for appending an amine-containing peptide based targeting group, namely, cRGDfK. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00027DOI Listing
February 2019

Therapeutic effect of RA223 in the management of breast cancer bone metastases.

Clin Ter 2019 Jan-Feb;170(1):e1-e3

Internal Medicine, Biomedical Department of Internal and Specialist Medicine, University of Palermo, Italy.

Radium 223 dichloride (Ra223) is the only targeted alpha therapy able to extend survival in patients with bone metastases from prostate cancer. Mechanism of action and data currently available focused mainly on osteoblastic metastases from prostate cancer. Phase 1 and 2 trials documented a clinical efficacy also in breast cancer patients with predominately bone disease, highlighting a reduction in alkaline phosphatase and other bone biomarkers. Read More

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http://dx.doi.org/10.7417/CT.2019.2100DOI Listing
February 2019

Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter.

Nucleic Acids Res 2019 Feb 21. Epub 2019 Feb 21.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

Long noncoding RNAs (lncRNAs) may either repress or activate HIV-1 replication and latency; however, specific mechanisms for their action are not always clear. In HIV-1 infected CD4+ T cells, we performed RNA-Sequencing (RNA-Seq) analysis and discovered an up-regulation of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an lncRNA previously described in cancer cells that associate with cancer pathogenesis. Moreover, we found that MALAT1 promoted HIV-1 transcription and infection, as its knockdown by CRISPR/Cas9 markedly reduced the HIV-1 long terminal repeat (LTR)-driven gene transcription and viral replication. Read More

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http://dx.doi.org/10.1093/nar/gkz117DOI Listing
February 2019

Novel mechanism of resistance to targeted therapies in lung cancer.

Mol Cell Oncol 2019 30;6(1):1551015. Epub 2018 Dec 30.

Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH USA.

We have identified a non-canonical role of0 Notch3 in response to epidermal growth factor receptor () tyrosine kinase inhibitor (TKI) therapy, whereby Notch3 associates with β-catenin, resulting in increased catenin beta-1 (CTNNB1, best known as β-catenin) stability and increased survival of drug persister cells (DPCs). Furthermore, combined treatment of an EGFR TKI with a β-catenin inhibitor demonstrated improved therapeutic outcomes in xenograft models. Read More

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http://dx.doi.org/10.1080/23723556.2018.1551015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370384PMC
December 2018

Indoleamine 2, 3-dioxygenase inhibitors in immunochemotherapy of breast cancer: challenges and opportunities.

Bioimpacts 2019 21;9(1):1-3. Epub 2018 Oct 21.

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Trafficking of macromolecular immunotherapy agent into the tumor microenvironment (TME) is a challenging issue. In the TME, cancer cells exploit indoleamine 2, 3-dioxygenase (IDO), as a cytosolic enzyme that catalyzes the L-tryptophan (Trp) through the kynurenine (Kyn) pathway, which could negatively regulate the activity of T cells. Thus, Trp/Kyn pathway, can be targeted with novel treatment modalities such as IDO1 inhibitor to benefit patients with aggressive solid tumors. Read More

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http://dx.doi.org/10.15171/bi.2019.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378097PMC
October 2018

Optimizing immobilization, margins, and imaging for lung stereotactic body radiation therapy.

Transl Lung Cancer Res 2019 Feb;8(1):24-31

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.

The simultaneous advancement of technologies for the delivery of precisely targeted radiation therapy and the paradigm shift to substantial hypofractionation have led to significant improvements in the treatment of early stage non-small cell lung cancer (ES-NSCLC). Stereotactic body radiation therapy (SBRT) has become a well-established option for the treatment of ES-NSCLC and is now becoming widely available within the radiation oncology community. Implementation of this technique, however, requires highly accurate target delineation, thorough evaluation of tumor motion, and improved on-board imaging at the time of treatment for patient alignment, each of which is critical for successful tumor control and mitigation of risks to normal tissues. Read More

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http://dx.doi.org/10.21037/tlcr.2018.09.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351403PMC
February 2019

Complete Response of Metastatic Melanoma to Local Radiation and Immunotherapy: 6.5 Year Follow-Up.

Cureus 2018 Dec 12;10(12):e3723. Epub 2018 Dec 12.

Radiation Oncology, Stanford University Medical Center, Stanford, USA.

The combined use of immunotherapy and radiation therapy is emerging as a potentially effective treatment for patients with immunogenic tumors such as melanoma; however, evidence for long-term treatment outcomes is lacking. Herein, we summarize our previously described case study of a patient with metastatic melanoma treated with two cycles of ipilimumab, followed by stereotactic body radiotherapy to two of seven liver metastases, with two additional cycles of ipilimumab. In the longest follow-up to date, we report a successful treatment outcome at 6. Read More

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http://dx.doi.org/10.7759/cureus.3723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373881PMC
December 2018

Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics.

Front Pharmacol 2019 6;10:79. Epub 2019 Feb 6.

Institute for Experimental Molecular Imaging, University Clinic, RWTH Aachen University, Aachen, Germany.

The retention and cellular internalization of drug delivery systems and theranostics for cancer therapy can be improved by targeting molecules. Since an increased uptake of riboflavin was reported for various cancers, riboflavin and its derivatives may be promising binding moieties to trigger internalization via the riboflavin transporters (RFVT) 1, 2, and 3. Riboflavin is a vitamin with pivotal role in energy metabolism and indispensable for cellular growth. Read More

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http://dx.doi.org/10.3389/fphar.2019.00079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372557PMC
February 2019

Iron-Chelated Polydopamine Decorated Doxorubicin-Loaded Nanodevices for Reactive Oxygen Species Enhanced Cancer Combination Therapy.

Front Pharmacol 2019 6;10:75. Epub 2019 Feb 6.

Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, China.

Combination therapy which enhances efficacy and reduces toxicity, has been increasingly applied as a promising strategy for cancer therapy. Here, a reactive oxygen species (ROS) that enhanced combination chemotherapy nanodevices was fabricated based on the Fe-chelated polydopamine (PDA) nanoparticles (NPs). The structure was characterized by dynamic light scattering-autosizer, transmission electron microscopy, energy dispersive spectroscopy, and Fourier-transform infrared (FT-IR) spectrophotometer. Read More

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http://dx.doi.org/10.3389/fphar.2019.00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372743PMC
February 2019

Focal Ablation of Prostate Cancer.

Rev Urol 2018 ;20(4):145-157

Department of Urology, NYU Langone Medical Center New York, NY.

The challenge to the urology community is to reduce the risks of screening and treatment by reducing the number of men undergoing unnecessary biopsy and whole-gland curative treatment of low-risk disease. There is compelling evidence that focal ablation of prostate cancer is truly minimally invasive and offers major functional advantages over whole-gland treatment. Read More

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http://dx.doi.org/10.3909/riu0809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375006PMC
January 2018

Discovery of inhibitors of membrane traffic from a panel of clinically effective anticancer drugs.

Biol Pharm Bull 2019 Feb 21. Epub 2019 Feb 21.

Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research.

In addition to their major targets, clinically effective drugs may have unknown off-targets. By identifying such off-targets it may be possible to repurpose approved drugs for new indications. We are interested in the Golgi apparatus as a novel target for cancer therapy, but there is a paucity of candidate Golgi-disrupting drugs. Read More

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http://dx.doi.org/10.1248/bpb.b18-01026DOI Listing
February 2019

Inhibition of Sphingosine Phosphate Receptor 1 Signaling Enhances the Efficacy of VEGF Receptor Inhibition.

Mol Cancer Ther 2019 Feb 20. Epub 2019 Feb 20.

Division of Hematology-Oncology, Beth Israel Deaconess Medical Center

Inhibition of vascular endothelial growth factor receptor (VEGFR) signaling is an effective treatment for renal cell carcinoma but resistance continues to be a major problem. Recently, the sphingosine phosphate (S1P) signaling pathway has been implicated in tumor growth, angiogenesis and resistance to antiangiogenic therapy. S1P is a bioactive lipid that serves an essential role in developmental and pathological angiogenesis via activation of the S1P receptor 1 (S1P1). Read More

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http://dx.doi.org/10.1158/1535-7163.MCT-18-0548DOI Listing
February 2019

Retrospective Analysis of Treatment Patterns and Effectiveness of Palbociclib and Subsequent Regimens in Metastatic Breast Cancer.

J Natl Compr Canc Netw 2019 Feb;17(2):141-147

Washington University School of Medicine, and St. Luke's Hospital, St. Louis, Missouri.

Cyclin-dependent kinase (CDK) 4/6 inhibitors are now the standard of care for hormone receptor-positive (HR+), HER2-negative (HER-) metastatic breast cancer (MBC). However, guidelines are lacking regarding their optimal sequencing with other available agents. This study examines physician practice patterns and treatment outcomes of palbociclib and subsequent therapies in a real-world setting. Read More

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http://dx.doi.org/10.6004/jnccn.2018.7094DOI Listing
February 2019

Disparities and Trends in Rates of Genetic Testing and Erlotinib Treatment Among Metastatic Non-Small Cell Lung Cancer Patients.

Cancer Epidemiol Biomarkers Prev 2019 Feb 20. Epub 2019 Feb 20.

Institute for Technology Assessment, Massachusetts General Hospital

Background: Despite reports of socioeconomic disparities in rates of genetic testing and targeted therapy treatment for metastatic non-small cell lung cancer (NSCLC), little is known about whether such disparities are changing over time.

Methods: We performed a retrospective analysis to identify disparities and trends in genetic testing and treatment with erlotinib. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified 9,900 stage 4 NSCLC patients diagnosed in 2007-2011 at age 65 or older. Read More

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http://dx.doi.org/10.1158/1055-9965.EPI-18-0917DOI Listing
February 2019

GSH-responsive anti-mitotic cell penetrating peptide-linked podophyllotoxin conjugate for improving water solubility and targeted synergistic drug delivery.

Bioorg Med Chem Lett 2019 Feb 6. Epub 2019 Feb 6.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China. Electronic address:

Podophyllotoxin (PPT) is a chemotherapeutic agent which has shown significant anti-cancer effects through inhibiting microtubule assembly. However, because of the poor water solubility and obvious side effects, PPT cannot be used in clinical cancer therapy. In order to solve these problems, a novel glutathione-responsive PPT conjugate has been synthesized in which PPT was linked to an anti-mitotic cell penetrating peptide (PRA) via a disulfide linkage. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.02.005DOI Listing
February 2019

The HGF-MET axis coordinates liver cancer metabolism and autophagy for chemotherapeutic resistance.

Autophagy 2019 Feb 20:1-22. Epub 2019 Feb 20.

b The Key Laboratory of Developmental Genes and Human Disease , Institute of Life Sciences, Southeast University , Nanjing , Jiangsu , China.

Notwithstanding the numerous drugs available for liver cancer, emerging evidence suggests that chemotherapeutic resistance is a significant issue. HGF and its receptor MET play critical roles in liver carcinogenesis and metastasis, mainly dependent on the activity of receptor tyrosine kinase. However, for unknown reasons, all HGF-MET kinase activity-targeted drugs have failed or have been suspended in clinical trials thus far. Read More

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http://dx.doi.org/10.1080/15548627.2019.1580105DOI Listing
February 2019

Nanoparticle Therapy for Vascular Diseases.

Arterioscler Thromb Vasc Biol 2019 Feb 21:ATVBAHA118311569. Epub 2019 Feb 21.

From the Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, CA (A.M.F., J.Y., K.-U.J., N.J.L.).

Nanoparticles promise to advance strategies to treat vascular disease. Since being harnessed by the cancer field to deliver safer and more effective chemotherapeutics, nanoparticles have been translated into applications for cardiovascular disease. Systemic exposure and drug-drug interactions remain a concern for nearly all cardiovascular therapies, including statins, antithrombotic, and thrombolytic agents. Read More

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http://dx.doi.org/10.1161/ATVBAHA.118.311569DOI Listing
February 2019

Coordinating Tissue Regeneration through TGF-β Activated Kinase 1 (TAK1) In-activation and Re-activation.

Stem Cells 2019 Feb 20. Epub 2019 Feb 20.

Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of TGF-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by re-activation to elicit differentiation and extracellular matrix (ECM) production. Read More

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http://dx.doi.org/10.1002/stem.2991DOI Listing
February 2019

Liver metastasis and Heng risk are prognostic factors in patients with non-nephrectomized synchronous metastatic renal cell carcinoma treated with systemic therapy.

PLoS One 2019 20;14(2):e0211105. Epub 2019 Feb 20.

Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang, Korea.

Objective: This study aimed to determine the prognostic factors of progression-free survival (PFS) and overall survival (OS) in non-nephrectomized patients with synchronous metastatic renal cell carcinoma (mRCC) receiving first-line vascular endothelial growth factor (VEGF)-targeted therapy or immunotherapy.

Methods: Of 70 patients, 57 (81.4%) were treated with targeted therapy, including 5 (7. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211105PLOS
February 2019

Assembly of upconversion nanophotosensitizer in vivo to achieve scatheless real-time imaging and selective photodynamic therapy.

Biomaterials 2019 Feb 13;201:33-41. Epub 2019 Feb 13.

Van 't Hoff Institute for Molecular Sciences. University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, the Netherlands. Electronic address:

A perfect "off" to "on" switch of the therapeutic function is very important to minimize the phototoxicity of nanoplatforms assisted imaging-guided photodynamic therapy (PDT) of cancer. Current approaches rely on preloaded photosensitizers, where the off/on state of PDT is regulated by the sensitizing light of photosensitizers. However, the photoactivities inevitably occur when imaging/diagnosis or exposure to sunlight, etc. Read More

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http://dx.doi.org/10.1016/j.biomaterials.2019.02.015DOI Listing
February 2019

Toward liquid biopsies in cancer treatment: application of circulating tumor DNA.

APMIS 2019 Feb 19. Epub 2019 Feb 19.

Center for Genomic Medicine, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.

Circulating tumor DNA (ctDNA) refers to the fraction of cell-free DNA in a patient's blood originating from tumor cells. Increased knowledge about tumor genomics, improvements in targeted therapies, and accompanying advances in DNA-sequencing technologies have increased the interest in using ctDNA as a minimally invasive tool in cancer diagnostics and treatment. Especially, early tumor detection including identification of minimal residual disease and stratification of adjuvant therapy are promising approaches. Read More

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http://dx.doi.org/10.1111/apm.12912DOI Listing
February 2019

EGFR-targeted therapy alters the tumor microenvironment in EGFR-driven lung tumors: Implications for combination therapies.

Int J Cancer 2019 Feb 5. Epub 2019 Feb 5.

Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Immune checkpoint inhibitors targeting the programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway have profoundly improved the clinical management of non-small-cell lung cancer (NSCLC). Nevertheless, the superiority of single-agent PD-1/PD-L1 inhibitors in pretreated EGFR mutant patients has turned out to be moderate. One proposed mechanism for poor response to immune checkpoint inhibitors is an immunosuppressive tumor microenvironment. Read More

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http://dx.doi.org/10.1002/ijc.32191DOI Listing
February 2019

Treatment Decisions for Metastatic Clear Cell Renal Cell Carcinoma in Older Patients: The Role of TKIs and Immune Checkpoint Inhibitors.

Drugs Aging 2019 Feb 20. Epub 2019 Feb 20.

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr, Suite 2161, Salt Lake City, UT, 84112, USA.

Given the underrepresentation of older patients in registration trials for metastatic renal cell carcinoma (mRCC), data to support the use of any particular systemic therapy over others, based on age, is limited. This is further complicated by clinical trials not commonly reporting adverse events by age. Thus, recommendations on treatment of older patients with mRCC are generally extrapolated from data on younger patients enrolled in these trials, which may not be ideal as many older patients are frail, have age-related organ dysfunction, or have multiple medical co-morbidities. Read More

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http://dx.doi.org/10.1007/s40266-019-00644-1DOI Listing
February 2019

Evaluation of apoptosis imaging biomarkers in a genetic model of cell death.

EJNMMI Res 2019 Feb 19;9(1):18. Epub 2019 Feb 19.

Cancer Imaging Centre, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.

Purpose: We have previously developed the caspase-based radiotracer, F-ICMT-11, for PET imaging to monitor treatment response. We further validated F-ICMT-11 specificity in a murine melanoma death-switch tumour model with conditional activation of caspase-3 induced by doxycycline.

Methods: Caspase-3/7 activity and cellular uptake of F-ICMT-11, F-ML-10 and F-FDG were assessed in B16ova and B16ovaRevC3 cells after death-switch induction. Read More

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http://dx.doi.org/10.1186/s13550-019-0487-8DOI Listing
February 2019

Targeted human cytolytic fusion proteins at the cutting edge: harnessing the apoptosis-inducing properties of human enzymes for the selective elimination of tumor cells.

Oncotarget 2019 Jan 25;10(8):897-915. Epub 2019 Jan 25.

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Patient-specific targeted therapy represents the holy grail of anti-cancer therapeutics, allowing potent tumor depletion without detrimental off-target toxicities. Disease-specific monoclonal antibodies have been employed to bind to oncogenic cell-surface receptors, representing the earliest form of immunotherapy. Targeted drug delivery was first achieved by means of antibody-drug conjugates, which exploit the differential expression of tumor-associated antigens as a guiding mechanism for the specific delivery of chemically-conjugated chemotherapeutic agents to diseased target cells. Read More

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http://dx.doi.org/10.18632/oncotarget.26618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368230PMC
January 2019

MicroRNA-708-5p affects proliferation and invasion of osteosarcoma cells by targeting URGCP.

Exp Ther Med 2019 Mar 15;17(3):2235-2241. Epub 2019 Jan 15.

Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

Osteosarcoma is an aggressive cancer of the skeletal system which remains a challenge for the current therapeutic strategies due to unclear etiology and molecular mechanisms of pathogenesis. The current study aimed to determine the expression levels, role and molecular mechanism of microRNA-708-5p (miR-708-5p) in the development of osteosarcoma. The expression level of miR-708-5p was detected using reverse transcription-quantitative polymerase chain reaction. Read More

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http://dx.doi.org/10.3892/etm.2019.7171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364217PMC

Therapeutic implications of germline genetic findings in cancer.

Nat Rev Clin Oncol 2019 Feb 19. Epub 2019 Feb 19.

Cancer Division, Garvan Institute of Medical Research, Sydney, Australia.

Cancer is a genetic disease. To date, translational cancer genomics has focused largely on somatic alterations, driven by the desire to identify targets for personalized therapy. However, therapeutically relevant information is also latent within the germline genome. Read More

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http://dx.doi.org/10.1038/s41571-019-0179-3DOI Listing
February 2019

Targeted delivery of IL2 to the tumor stroma potentiates the action of immune checkpoint inhibitors by preferential activation of NK and CD8+ T cells.

Cancer Immunol Res 2019 Feb 19. Epub 2019 Feb 19.

Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich)

Recombinant human interleukin-2 (IL2) is being considered as a combination partner for immune checkpoint inhibitors in cancer therapy, but the product only has a narrow therapeutic window. Therefore, we used F8-IL2, an antibody-IL2 fusion protein capable of selective localization to the tumor site, in combination with antibodies against murine CTLA-4, PD-1, and PD-L1. In immunocompetent mice bearing CT26 tumors, the combination of F8-IL2 with CTLA-4 blockade was efficacious, leading to increased progression-free survival and protective immunity against subsequent tumor re-challenges. Read More

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http://dx.doi.org/10.1158/2326-6066.CIR-18-0566DOI Listing
February 2019