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Histopathology 2019 Apr 23. Epub 2019 Apr 23.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

Aims: Secretory carcinoma of the breast (SCB) is a rare histologic type of breast carcinoma with a generally indolent clinical behavior. We aim to elucidate the clinical, pathological and molecular findings of SCB cases and identify characteristics associated with aggressive clinical courses.

Methods And Results: Fourteen patients with SCB were identified, including 12 women and 2 men, with a median age of 56 years (range, 8-81 years). Read More

J Cell Physiol 2019 Apr 22. Epub 2019 Apr 22.

Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.

The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-1. Read More

Australas J Dermatol 2019 Apr 22. Epub 2019 Apr 22.

Flinders Medical Centre, Bedford Park, South Australia, Australia.

Squamous cell carcinoma incidence is 65- to 250-fold in solid organ transplant recipients, BCC is 10-fold and in Australia, rates of skin cancer in solid organ transplant recipients reach 70-82% prevalence within the first 20 years; hence, effective, evidence-based treatment of early and precancerous lesions is an essential tool in dermatological patient care. Photodynamic therapy is used to treat a range of conditions including actinic keratoses, squamous cell carcinoma in situ, superficial basal cell carcinoma and nodular basal cell carcinoma. A literature review was undertaken to examine the outcomes of photodynamic therapy in solid organ transplant recipients and methods of optimising outcomes in solid organ transplant recipients. Read More

Brain Tumor Pathol 2019 Apr 22. Epub 2019 Apr 22.

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Here, we report a highly unusual case of high-grade glioneuronal tumor with a neurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. Read More

Cureus 2019 Feb 8;11(2):e4038. Epub 2019 Feb 8.

Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, USA.

Skin cancer is the most commonly diagnosed malignancy in the United States, and invasive cutaneous melanoma is responsible for the vast majority of skin cancer-related deaths. Treatment options for patients with regional nodal disease, in-transit metastases, or locally advanced or distant metastatic disease are challenging. Historically survival rates in this patient population are dismal. Read More

Case Rep Oncol 2019 Jan-Apr;12(1):241-247. Epub 2019 Mar 19.

Orlando Health Department of Pathology, Orlando, Florida, USA.

Ovarian carcinosarcoma is also referred to as malignant mixed Mullerian tumor (MMMT). It is a rare neoplasm, and although it represents less than 5% of malignant ovarian tumors, it remains generally well-known among clinicians and pathologists. Rarer yet is ovarian teratoid carcinosarcoma, defined as carcinosarcoma with the added feature of immature neuroectodermal tissue, with or without elements of primitive germ cell tumor. Read More

Nat Med 2019 Apr 22. Epub 2019 Apr 22.

Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Cancer treatments have evolved from indiscriminate cytotoxic agents to selective genome- and immune-targeted drugs that have transformed the outcomes of some malignancies. Tumor complexity and heterogeneity suggest that the 'precision medicine' paradigm of cancer therapy requires treatment to be personalized to the individual patient. To date, precision oncology trials have been based on molecular matching with predetermined monotherapies. Read More

Blood 2019 Apr 22. Epub 2019 Apr 22.

Department of Internal Medicine III, University of Ulm, Germany

Targeted therapy is currently revolutionizing the treatment of cancers, but resistance evolves against these therapies and derogates their success. The PI3K-δ inhibitor idelalisib has been approved for CLL and NHL treatment, but the mechanisms conferring resistance in a subset of patients are unknown. Here, we modelled resistance to PI3K-δ inhibitor using a serial tumor transfer and treatment scheme in mice. Read More

Clin Cancer Res 2019 Apr 22. Epub 2019 Apr 22.

Pathology, Johns Hopkins University.

Purpose: Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well-characterized.

Experimental Design: To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and non-gestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including 5 gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (2-3 different components each) and 6 pure choriocarcinomas, for somatic mutations, single nucleotide polymorphisms and PD-L1 expression. Read More

Eur Urol Focus 2019 Apr 19. Epub 2019 Apr 19.

Division of Medical Oncology, Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Canada. Electronic address:

One of the major challenges of personalized oncology lies in identifying predictive biomarkers of response to therapy that are practical in the clinical setting. Although many new targeted and immune-based treatments have emerged in recent years as effective systemic therapy options in metastatic renal cell carcinoma (mRCC), optimizing the selection and sequencing of treatments for any individual patient with this disease remains a significant challenge. The CheckMate-214 trial demonstrated that the International mRCC Database Consortium risk model is an effective predictive biomarker in the first-line treatment of mRCC. Read More

Biochem Biophys Res Commun 2019 Apr 19. Epub 2019 Apr 19.

National Translational Science Center for Molecular Medicine, Air Force Medical University, Xi'an, 710032, China; Department of Cell Biology, School of Basic Medicine, Air Force Medical University, Xi'an, 710032, China. Electronic address:

Cluster of differentiation 147 (CD147), a transmembrane protein of the immunoglobulin superfamily, is a potential target of treatment against human non-small cell lung cancer (NSCLC). Although there have been exciting advances in epidermal growth factor receptor (EGFR)-targeted therapy for NSCLC in recent years, additional novel targeted agents are needed to improve the efficiency and to offer more options for patients. Antibody-drug conjugates (ADCs) utilize a chemical linker to conjugate cytotoxic drugs to a monoclonal antibody to maximize the delivery to target cells and minimize the delivery to other normal cells. Read More

Expert Opin Investig Drugs 2019 Apr 22:1-7. Epub 2019 Apr 22.

b Division of Molecular Pathology , Institute of Cancer Research , London , UK.

Introduction: Liposarcomas (LPS) are a heterogeneous group of adipocytic soft tissue sarcomas with limited treatment options in the advanced/metastatic setting. Pazopanib is a multi-target tyrosine kinase inhibitor (TKI) with anti-angiogenic and antitumorigenic properties. Whilst targeted agents including TKIs have been extensively studied in other solid tumors and the sarcoma subtype gastrointestinal stromal tumor (GIST), we currently lack effective treatments for the liposarcoma subtype. Read More

Cutan Ocul Toxicol 2019 Apr 22:1-27. Epub 2019 Apr 22.

b Department of Dermatology and Venereology , Abdurrahman Yurtaslan Oncology Training and Research Hospital , Ankara , Turkey.

Background: Papulopustular rash is the most common cutaneous adverse effect during targeted tumour therapy particularly with epidermal growth factor receptor inhibitors (EGFRIs).

Objective: To evaluate the adverse skin reactions, mainly papulopustular rash, caused by targeted tumour therapy.

Materials And Methods: We retrospectively analyzed the data of patients who were diagnosed papulopustular rash due to targeted chemotherapeutic agents between January-2016 and August-2018. Read More

Cancers (Basel) 2019 Apr 21;11(4). Epub 2019 Apr 21.

Cancer and Stem Cell Biology Group, School of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK.

Cell therapy is a promising new treatment option for cancer. In particular, mesenchymal stem cells (MSCs) have shown potential in delivering therapeutic genes in various tumour models and are now on the verge of being tested in the clinic. A number of therapeutic genes have been examined in this context, including the death ligand TRAIL. Read More

Medicine (Baltimore) 2019 Apr;98(16):e15245

Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning.

Rationale: Urothelial carcinoma, also named transitional cell carcinoma, is the most frequent occurring malignancy in the urinary system. It mainly invades the surrounding tissues and metastasizes to distant organs in later stages.

Patient Concerns: Here, we presented an unusual case of occult urothelial carcinoma primarily manifested as a multiorgan metastatic cancer in a 59-year-old man. Read More

Am J Ther 2019 Apr 16. Epub 2019 Apr 16.

Division of Cardiology, Westchester Medical Center, New York Medical College, Valhalla, NY.

Background: Immunotherapy is a significant breakthrough in cancer therapy in the last decade. Immunotherapy is better tolerated compared with chemotherapy. However, it does have side effects, and one of the rare and serious side effects of immunotherapy is cardiotoxicity. Read More

Int J Cancer 2019 Apr 22. Epub 2019 Apr 22.

Institute of Pathology, University Hospital Heidelberg, Germany.

Next-generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool in translational oncology. Its rapidly increasing use during the last decade has expanded the options for targeted tumor therapies, and molecular tumor boards have grown accordingly. However, with increasing detection of genetic alterations, their interpretation has become more complex and error-prone, potentially introducing biases and reducing benefits in clinical practice. Read More

Comput Struct Biotechnol J 2019 26;17:447-453. Epub 2019 Mar 26.

Department of Haematology and Oncology, Medical University of Innsbruck, Austria.

In this review we aim to summarize studies investigating the impact of a molecular profiling (MP)-guided treatment approach in heavily pretreated cancer patients. In summary, many independent single- and multicenter studies showed a significant benefit of MP-guided treatment regarding response rates and survival. However, in the only randomized trial conducted so far, no benefit of MP-guided targeted therapy was observed. Read More

Oncotarget 2019 Mar 12;10(21):2012-2021. Epub 2019 Mar 12.

Department of Gynecologic Oncology, Azienda Ospedaliera Brotzu, Cagliari, Italy.

Background: The treatment of patients with multiple synchronous tumors is challenging and complex. The use of next generation sequencing (NGS) may help in identification of germline mutations in genes involved in a common etiology for both tumors thus allowing a common effective therapeutic strategy.

Patients And Methods: We describe the unexpected positive results obtained in a young woman with relapsed chemo-resistant stage IVB cervical and synchronous stage IV lung cancer, who underwent an interdisciplinary approach including palliative surgery with laparoscopic total pelvic exenteratio followed by a chemo-immunotherapy protocol with the anti-Programmed Death (PD)-1 antibody nivolumab plus metronomic cyclophosphamide. Read More

Ann Dermatol Venereol 2019 Apr 18;146(4):326-339. Epub 2019 Apr 18.

Service de dermatologie pédiatrique et dermatologie, Centre de référence des maladies rares de la peau, Hôpital pédiatrique, Groupe hospitalier Pellegrin, Centre hospitalier universitaire de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux cedex, France. Electronic address:

Many types of genodermatosis exist, with numerous modes of transmission. The development of molecular genetic methods, in particular the most recent sequencing techniques, can be used to identify an increasing number of genes involved in these forms of genodermatosis while providing confirmation or more details regarding clinical diagnosis. Thanks to this approach, it is possible to determine risk of recurrence and to formulate an antenatal strategy. Read More

Breast Cancer Res Treat 2019 Apr 20. Epub 2019 Apr 20.

Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, USA.

Purpose: Primary breast and prostate cancers can be cured, but metastatic disease cannot. Identifying cell factors that predict metastatic potential could guide both prognosis and treatment.

Methods: We used Cell-SELEX to screen an RNA aptamer library for differential binding to prostate cancer cell lines with high vs. Read More

Drug Resist Updat 2019 Apr 9;43:10-28. Epub 2019 Apr 9.

Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, United States. Electronic address:

Recent advances in the treatment of various cancers have resulted in the adaptation of several novel immunotherapeutic strategies. Notably, the recent intervention through immune checkpoint inhibitors has resulted in significant clinical responses and prolongation of survival in patients with several therapy-resistant cancers (melanoma, lung, bladder, etc.). Read More

Gene 2019 Apr 17. Epub 2019 Apr 17.

Laboratory of Genetics and Molecular Pathology, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II, Casablanca 20250, Morocco.

The study of EGFR gene mutational profile in NSCLC patients has a special clinical significance in the selection of patients for tyrosine-kinase inhibitors therapy. From 2017, the targeted therapy started to be accessible in public sector in Morocco, thus, the implementation of techniques for the molecular characterization of EGFR mutations in the laboratories became a necessity. The aim of this study was to present targeted methods "ADx-ARMS technology and the Idylla™ system" for the identification of EGFR mutational profile, methods that can be implemented in our clinical laboratories for routine analysis instead of outsourcing analysis to other countries. Read More

Adv Drug Deliv Rev 2019 Apr 17. Epub 2019 Apr 17.

School of Pharmacy, The Faculty of Medical Sciences, King George VI Building, Newcastle University, Newcastle upon Tyne NE1 7RU, UK; Division of Stratified Medicine, Biomarkers & Therapeutics, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Electronic address:

Redirecting the recognition specificity of T lymphocytes to designated tumour cell surface antigens by transferring chimeric antigen receptor (CAR) genes is becoming an effective strategy to combat cancer. Today, CAR T-cell therapy has proven successful in the treatment of haematological malignancies and the first CD19 CAR T-cell products has already entered the market. This success is expanding CAR design for broader malignancies including solid tumours. Read More

Cancer Med 2019 Apr 19. Epub 2019 Apr 19.

Department of Surgery in Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai, China.

Nearly 75% of breast cancers are hormone receptor-positive (HR+) and human epidermal growth factor receptor type 2-negative (HER2-), making endocrine therapy the mainstay of treatment for HR+ and HER2- combination. Although endocrine therapy, such as therapy with fulvestrant, is widely used in the clinic, endocrine resistance (primary or secondary) is inevitable and poses a serious clinical concern. However, the therapeutic landscape of HR+/HER2- breast cancer is rapidly changing and evolving. Read More

J Appl Clin Med Phys 2019 Apr 19. Epub 2019 Apr 19.

Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.

Purpose: Transrectal ultrasound images are routinely acquired for low dose rate (LDR) prostate brachytherapy dosimetric preplanning (pTRUS), although diagnostic multiparametric magnetic resonance imaging (mpMRI) may serve this purpose as well. We compared the predictive abilities of TRUS vs MRI relative to intraoperative TRUS (iTRUS) to assess the role of mpMRI in brachytherapy preplanning.

Materials And Methods: Retrospective analysis was performed on 32 patients who underwent iTRUS-guided prostate LDR brachytherapy as either mono- or combination therapy. Read More

Int J Pharm 2019 Apr 16. Epub 2019 Apr 16.

School of Biological Science and Engineering, South China University of Technology, Guangzhou 510640, China; Wenzhou Institute of Biomaterials and Engineering, CNITECH, Chinese Academy of Sciences, Wenzhou, Zhejiang Province, 325001, PR China. Electronic address:

Nanoparticles (NPs) conjugated with aptamers have been extensively in recent years, which can efficiently target cancer cells that improve the therapeutic effect. Aptamers (Apt) are small oligonucleotide molecule ligands have specific high-affinity. In this work, we developed a PEG-PLGA nanoparticles (NPs) encapsulated with doxorubicin. Read More

Life Sci 2019 Apr 16. Epub 2019 Apr 16.

Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

We previously showed that folate liposomes of 5FU made from Dipalmitoylphosphatidylcholine (DPPC) induced cell death in HT-29 and HeLa cells more potently than bulk 5FU. Also, a primary 5FU liposomal formulation with phosphatidyl choline (PC) exhibited higher cytotoxicity in murine colon cancer cells. In the present study, optimization of 5FU PC liposome, mechanism of cell death induction in human cancer cell lines and its safety along with other assays have been employed for targeted PC liposomes of 5FU. Read More

Cancer Biol Ther 2019 Apr 19:1-13. Epub 2019 Apr 19.

a Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences , Wenzhou Medical University , Wenzhou , Zhejiang , China.

Prostate cancer (PCa) is the second frequently newly diagnosed cancer in men. Androgen deprivation therapy has been widely used to inhibit PCa growth but eventually fails in many patients. Androgen receptor and its downstream molecules like microRNAs could be promising therapeutic targets. Read More

JAMA Netw Open 2019 Apr 5;2(4):e192561. Epub 2019 Apr 5.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.

Importance: There has been significant recent interest in understanding the utility of quantitative imaging to delineate breast cancer intrinsic biological factors and therapeutic response. No clinically accepted biomarkers are as yet available for estimation of response to human epidermal growth factor receptor 2 (currently known as ERBB2, but referred to as HER2 in this study)-targeted therapy in breast cancer.

Objective: To determine whether imaging signatures on clinical breast magnetic resonance imaging (MRI) could noninvasively characterize HER2-positive tumor biological factors and estimate response to HER2-targeted neoadjuvant therapy. Read More

Expert Opin Biol Ther 2019 Apr 19. Epub 2019 Apr 19.

d Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine , Baltimore , MD , USA.

Introduction: The systemic treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the identification of actionable mutations and the use of targeted agents. Unfortunately, many tumors will acquire resistance and >75% of NSCLC cases lack for an actionable gene aberration. In this setting, immunotherapy rises as effective therapeutic where immune checkpoint inhibitors have entered or are entering the market in many neoplasms, including NSCLC. Read More

J Cell Physiol 2019 Apr 18. Epub 2019 Apr 18.

Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Gene therapy using biocompatible cationic liposomes is amongst promising approaches that decreases death from cancers. Here an invasive multidrug resistant cell model has been developed by lentiviral transfection. In parallel phospholipids have been covalently conjugated to TAT, MMP2, and Herceptin. Read More

Case Rep Urol 2019 14;2019:7102504. Epub 2019 Mar 14.

Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA.

Renal cell carcinoma, particularly the most common clear cell type, is one of the most aggressive of urological cancers with significant risk of metastatic spread. It also has a propensity for venotropism with a proportion of tumors developing thrombi up to the right atrium. The response with newly adopted targeted therapy has been considered to be in the evolutionary stage with no clear role with respect to debulking or reducing the size of the inferior vena cava (IVC) thrombus. Read More

Stem Cells Int 2019 14;2019:8108576. Epub 2019 Mar 14.

Department of Obstetrics and Gynecology, The First Affiliated Hospital, Key laboratory of Follicular Development and Reproductive Health of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.

MicroRNAs (miRNAs) are potential therapeutic targets in endometrial cancer, but the difficulties associated with their delivery to tumor target cells have hampered their applications. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a well-recognized tumor-homing ability, emphasizing the capacity of tumor-targeted delivery of extracellular vesicles. hUCMSCs release extracellular vesicles rich in miRNAs, which play a vital role in intercellular communication. Read More

Oncogenesis 2019 Apr 18;8(5):30. Epub 2019 Apr 18.

Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, 453003, Xinxiang, Henan, P.R. China.

Breast cancer ranks no. 1 in women cancer worldwide, while 60-70% are estrogen receptor alpha positive. The estrogen selective modulators, such as tamoxifen, become the effective drugs for controlling ER alpha breast cancer progression. Read More

Cancer Res 2019 Apr 18. Epub 2019 Apr 18.

University Hospital and University of Zurich

Oncogenic MYC activation promotes proliferation in Burkitt lymphoma (BL), but also induces cell cycle arrest and apoptosis mediated by p53, a tumor suppressor that is mutated in 40% of BL cases. To identify molecular dependencies in BL, we performed RNAi-based, loss-of-function screening in eight BL cell lines and integrated non-BL RNAi screens and genetic data. We identified 76 genes essential to BL, including genes associated with hematopoietic cell differentiation (FLI1, BCL11A) or B cell development and activation (PAX5, CDKN1B, JAK2, CARD11) and found a number of context-specific dependencies including oncogene addiction in cell lines with TCF3/ID3 or MYD88 mutation. Read More

Clin Genitourin Cancer 2019 Mar 27. Epub 2019 Mar 27.

Department of Health Policy and Administration, Pennsylvania State University, University Park, PA; Department of Public Health Sciences, Pennsylvania State University, Hershey, PA; Department of Surgery, Penn State College of Medicine, Hershey, PA.

Purpose: To estimate the association between a hospital's risk-adjusted emergency department (ED) visit rate and its risk-adjusted mortality rate and costs among kidney cancer patients undergoing initial nephrectomy.

Patients And Methods: Using 2007-2012 Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we used logistic regression to model ED visit occurrence within 30 and 365 days for all kidney cancer patients receiving initial surgery. Our model controlled for demographics, stage, histology, systemic targeted therapy, and comorbidities. Read More

J Immunother Cancer 2019 Apr 18;7(1):110. Epub 2019 Apr 18.

Department of Cardiothoracic Surgery, Division of Thoracic and Foregut Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Malignant pleural effusions (MPE) are a common terminal pathway for many cancers, with an estimated United States incidence of more than 150,000 cases per year. MPE is an aggressive disease with a uniformly fatal prognosis and a life expectancy of only 3 to 12 months. The development of an effective targeted therapy represents a pressing unmet need. Read More

Int J Mol Sci 2019 Apr 17;20(8). Epub 2019 Apr 17.

Medical Oncology Department, The Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, 28034 Madrid, Spain.

Clear cell renal cell carcinoma (ccRCC) is the seventh most frequently diagnosed tumor in adults in Europe and represents approximately 2.5% of cancer deaths. The molecular biology underlying renal cell carcinoma (RCC) development and progression has been a key milestone in the management of this type of tumor. Read More

Anticancer Drugs 2019 Apr 16. Epub 2019 Apr 16.

Institute of Life Sciences.

Ovarian cancer is a heterogeneous disease with complex molecular and genetic hallmarks. Benefitting from profound understanding of molecular mechanisms in ovarian cancer pathogenesis, novel targeted drugs have been actively explored in preclinical studies and clinical trials. Considered as one of the most potent and effective targeted therapies for the treatment of ovarian cancer, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) take advantages of synthetic lethality mechanisms to prevent DNA damage repair in cancer cells and cause their death, especially in cancers with BRCA mutations. Read More

Future Med Chem 2019 Apr 18. Epub 2019 Apr 18.

Department of Pharmacy & Biotechnology, Alma Mater Studiorum University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.

Lysine methyltransferases SMYD2 and SMYD3 are involved in the epigenetic regulation of cell differentiation and functioning. Overexpression and deregulation of these enzymes have been correlated to the insurgence and progression of different tumors, making them promising molecular targets in cancer therapy even if their role in tumors is not yet fully understood. In this light, selective small-molecule inhibitors are required to fully understand and validate these enzymes, as this is a prerequisite for the development of successful targeted therapeutic strategies. Read More

Mol Ther Methods Clin Dev 2019 Jun 16;13:371-379. Epub 2019 Mar 16.

Division of Molecular Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.

Chimeric antigen receptor (CAR)-modified T cells have revealed promising results in the treatment of cancer, but they still need to overcome various hurdles, including a complicated manufacturing process. Receptor-targeted lentiviral vectors (LVs) delivering genes selectively to T cell subtypes may facilitate and improve CAR T cell generation, but so far they have resulted in lower gene delivery rates than conventional LVs (vesicular stomatitis virus [VSV]-LV). To overcome this limitation, we studied the effect of the transduction enhancer Vectofusin-1 on gene delivery to human T cells with CD4- and CD8-targeted LVs, respectively, encoding a second-generation CD19-CAR in conjunction with a truncated version of the low-affinity nerve growth factor receptor (ΔLNGFR) as reporter. Read More

ESMO Open 2018 7;3(Suppl 1):e000462. Epub 2019 Feb 7.

Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

Cervical cancer continues to be a common cancer in women worldwide, especially in less developed regions where advanced stage presentations are common. Addition of bevacizumab to cytotoxic chemotherapy has been the only notable recent advance in the treatment of recurrent and metastatic cervical cancer. Outcomes in patients with locally advanced disease have also plateaued after meaningful gains were achieved with concomitant chemoradiation treatment. Read More

Chem Sci 2019 Apr 21;10(13):3779-3785. Epub 2019 Feb 21.

Key Laboratory of Flexible Electronics (KLOFE) , Institute of Advanced Materials (IAM) , School of Physical and Mathematical Science , Nanjing Tech University (NanjingTech) , 30 South Puzhu Road , Nanjing 211800 , China . Email: ; Email: ; Email:

Organelle-targeting nanosystems are envisioned as promising tools for phototherapy, which can generate heat or reactive oxygen species (ROS) induced cytotoxicity in the targeted location but leave the surrounding biological tissues undamaged. In this work, an imaging-guided mitochondria-targeting photothermal/photodynamic nanosystem has been developed on the basis of functionalized black phosphorus (BP) nanosheets (NSs). In the nanosystem, BP NSs are coated with polydopamine (PDA) and then covalently linked with both chlorin e6 (Ce6) and triphenyl phosphonium (TPP) through carbodiimide reaction between the amino group and the carboxyl group, forming BP@PDA-Ce6&TPP NSs. Read More

Lab Invest 2019 Apr 17. Epub 2019 Apr 17.

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Triple negative breast cancer (TNBC) is responsible for significant number of breast cancer-associated deaths because of lacking of successful molecular-targeted therapy. To explore a therapeutic target for TNBC, we performed a siRNA-mediated knockdown screening and identified Polo-like kinase 1 (PLK1) as a potential therapeutic target for TNBC. Knockdown of PLK1 as well as a small compound inhibitor for PLK1, BI-2536, induced G2/M arrest and created polyploid cell population, shown by increased DNA content and nuclear size. Read More

Gynecol Oncol 2019 Apr 14. Epub 2019 Apr 14.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Immunotherapy (IO) is an important new pillar in the treatment of solid tumors, and the integration of IO agents with chemotherapy, targeted therapy, surgery and radiation has yet to be defined. As preclinical and clinical studies have described synergistic activity with the combination of radiation and immunotherapy, many clinical trials are underway to explore both the safety and efficacy of this approach both in the metastatic and definitive setting. Through immune priming, radiation may enhance local tumor control at the irradiated site, as well as induce a systemic response to control distant metastasis, known as the abscopal effect. Read More

Ther Adv Cardiovasc Dis 2019 Jan-Dec;13:1753944719843435

Department of Medicine, Hematology Oncology Division, University of Florida, Gainesville, FL, USA.

The emergence of various targeted anticancer agents has led us to uncharted territory secondary to their cardiotoxic potential with many burning questions, which in turn has led to the evolution of the cardio-oncology field. These targeted agents differ in their cardiovascular complication (CVC) potential even within the same class and it is very difficult to design screening tests that can predict CVCs. Moreover, there is a need for more research to answer many crucial questions, since these toxicities are unanticipated and can lead to poor overall survival of cancer patients. Read More

Klin Onkol 2019 ;32(2):97-100

Background: With advancements in diagnostic techniques, oligometastatic prostate cancer is diagnosed in patients who were, in the past, considered to have localized disease. Moreover, evidence of the effectiveness of treatment intensification for this disease is increasing, focusing on primary tumors as well as metastatic lesions. Thus, we can delay the start of systemic palliative treatment and improve overall survival. Read More

Cell Rep 2019 Apr;27(3):806-819.e5

Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

KRAS is one of the driver oncogenes in non-small-cell lung cancer (NSCLC) but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and enables their proliferation. Two MEKis, selumetinib and trametinib, induce T cell activation with increased CTLA-4 expression and, to a lesser extent, PD-1 expression on T cells in vivo after cyclical pulsatile MEKi treatment. Read More