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Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st-3rd, 2022-Naples, Italy).

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have se

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… Poulikakos (PIP): research funding from Black Diamond Therapeutics, Verastem Onc. Jeffrey S. …

Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial.

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed o

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… P.Y.W. has received research support from Astra Zeneca/MedImmune, Beigene, Celgene, Chimerix, Eli Lilly, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Puma, Servier, Vascular Biogenics and VBI Vaccines; is on the advisory board of AstraZeneca, Bayer, Black Diamond, Boehringer Ingelheim …

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren's syndrome: evidence- and practice-based guidance.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice

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… BMJ Open ( 2019 ) 9 ( 12 ): e032569 . doi: 10.1136/bmjopen-2019-032569 PMC6937022 31848169 67 Teng YKO Bruce IN Diamond B Furie RA van Vollenhoven RF Gordon D . phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination …

Cannabis, One Health, and Veterinary Medicine: Cannabinoids' Role in Public Health, Food Safety, and Translational Medicine.

Public health is connected to cannabis with regard to food, animal feed (feed), and pharmaceuticals. Therefore, the use of phytocannabinoids should be examined from a One Health perspective. Current knowledge on medical cannabis treatment (MCT) does not address sufficiently diseases which are of epidemiological and of zoonotic concern. The use of cannabinoids in veterinary medicine is illegal in most countries, mostly due to lack of evidence-based medicine. To answer the growing need of scientific evidence-based applicable medicine in both human and veterinary medicine, a new approach for the

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… Diamond in the roughage: can foods prevent and treat disease? Pharm J. 2016;296:25–8. doi: 10.1211/PJ.2016.20200551. 39. Albini A, Bassani B, Baci D, et al. Nutraceuticals and “repurposed” drugs of phytochemical origin in prevention and interception of chronic degenerative diseases and cancer. …

Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies.

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the main

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… Diamond J.R. Younger A. Messersmith W.A. Adriaens L. Liu L. Kao R.J. DiCioccio A.T. A phase I first-in-human study of enoticumab (REGN421), a fully human delta-like ligand 4 (Dll4) monoclonal antibody in patients with advanced solid tumors Clin. …

Myeloma bone disease: Pathophysiology and management.

Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases t

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… Diamond T, Levy S, Day P, Barbagallo S, Manoharan A, Kwan YK. Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity. …

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intra

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… Vanpouille-Box C, Diamond JM, Pilones KA, et al. TGFβ is a master regulator of radiation therapy-induced anti-tumor immunity. Cancer Res. 2015;75(11): 2232–42. …

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identify

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… Schlimgen R, Howard J, Wooley D, Thompson M, Baden LR, Yang OO, Christiani DC, Mostoslavsky G, Diamond DV, Duane EG, et al. Risks associated with lentiviral vector exposures and prevention strategies. J Occup Environ Med. 2016;58:1159–66. 156. Rossetti M, Cavarelli M, Gregori S, Scarlatti G. …

Multiple myeloma, a quintessential malignant disease of aging: a geroscience perspective on pathogenesis and treatment.

Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted

Beyond Clinical Trials in Patients With Multiple Myeloma: A Critical Review of Real-World Results.

The current strategies for the treatment of multiple myeloma (MM) have improved, thanks to effective drug classes and combination therapies, for both the upfront and relapsed settings. Clinical trials for newly diagnosed transplant-ineligible patients led to the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) in combination with anti-CD38 monoclonal antibodies (mAbs), to be administered during the induction phase before transplantation and during maintenance treatment, with lenalidomide recommended until relapse. In relapsed/refractory patients, the complex treatment

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… Tan C, Diamond B, Hultcrantz M, Korde N, Lesokhin AM, Mailankody S, et al. …

Modern therapeutic approaches in cholangiocarcinoma: A narrative review of key biomarkers and clinical trials.

Cholangiocarcinoma (CCA), the second most common hepatic malignancy after hepatocellular carcinoma, presents a significant clinical challenge. This epithelial cell malignancy occurs in various anatomical subtypes, including intrahepatic, perihilar, and distal, each associated with unique genetic aberrations, clinical presentations, and treatment options. Early diagnosis is challenging, leading to poor survival rates, especially in advanced cases. Precision medicine offers hope for improved management of CCA by tailoring treatments based on molecular profiling. In recent years, the investigatio

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… Diamond S. DiMatteo D. INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models PloS One 15 4 2020 e0231877 10.1371/journal.pone.0231877 PMC7313537 32315352 99 Necchi A. Pouessel D. …

От статического риска до динамического мониторинга заболеваний: роль MRD и иммунного профилирования в множестве миелом.

Терапевтический ландшафт множественной миеломы (ММ) претерпел глубокие изменения, при этом высокоэффективные комбинированные режимы и иммунная терапия позволили обеспечить беспрецедентные темпы глубоких и устойчивых ответных мер. В результате этого одной традиционной стратификации базовых рисков становится все более недостаточно для объяснения неоднородности клинических результатов или для направления лечения на протяжении всего курса лечения. Эта эволюционирующая парадигма сместила внимание на динамическое, адаптированное к реакциям наблюдение за заболеваниями, сосредоточенное на поддающихся

Bispecific antibody targets and therapies in multiple myeloma.

Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be low

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… Kowalski A, Lykon JL, Diamond B, Coffey D, Kaddoura M, Maura F, et al. Tocilizumab prophylaxis for patients treated with teclistamab: A single-center experience. Blood. (2023) 142:4709–9. doi: 10.1182/blood-2023-187086 55. Kumar S, Bachier CR, Cavo M, Corradini P, Delforge M, Janowski W, et al. …

Applications of Curcumin and Its Nanoforms in the Treatment of Cancer.

Due to the diverse medicinal and pharmacokinetic properties of turmeric, it is well-known in the therapeutic, pharmaceutic, nutraceutical, cosmetic, and dietary industries. It gained importance due to its multitude of properties, such as wound-healing, anti-inflammatory, anti-oxidant, anti-microbial, cytoprotective, anti-aging, anti-cancer, and immunomodulatory effects. Even though the natural healing effect of turmeric has been known to Indians as early as 2500 BCE, the global demand for turmeric has increased only recently. A major reason for the beneficiary activities of turmeric is the pre

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… Diamond T.H. Badmaev V. Manoharan A. Ramakrishna R. The Potential Role of Curcumin in Patients with Monoclonal Gammopathy of Undefined Significance—Its Effect on Paraproteinemia and the Urinary N-Telopeptide of Type I Collagen Bone Turnover MarkerThe Role of Curcumin in MGUS Clin. …

Recombinant Interferon-β in the Treatment of Polycythemia Vera and Related Neoplasms: Rationales and Perspectives.

About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians. Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntr

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… Lazear H.M., Schoggins J.W., Diamond M.S. Shared and Distinct Functions of Type I and Type III Interferons. Immunity. 2019;50:907–923. doi: 10.1016/j.immuni.2019.03.025. 124. Borden E.C. Interferons α and β in cancer: Therapeutic opportunities from new insights. Nat. Rev. …

Nanoparticle-Based RNAi Therapeutics Targeting Cancer Stem Cells: Update and Prospective.

Cancer stem cells (CSCs) are characterized by intrinsic self-renewal and tumorigenic properties, and play important roles in tumor initiation, progression, and resistance to diverse forms of anticancer therapy. Accordingly, targeting signaling pathways that are critical for CSC maintenance and biofunctions, including the Wnt, Notch, Hippo, and Hedgehog signaling cascades, remains a promising therapeutic strategy in multiple cancer types. Furthermore, advances in various cancer omics approaches have largely increased our knowledge of the molecular basis of CSCs, and provided numerous novel targ

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… Diamond J.R. Becerra C. Richards D. Mita A. Osborne C. O'Shaughnessy J. Zhang C. Henner R. Kapoun A.M. Xu L. Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer Breast Cancer Res. …

The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively.

IntroductionTraditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers.MethodBy reviewing published literature and the current progress of ADCs, we aimed to summarize the basic characteristics, clinical progress, and challenges of

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… Kalinsky K, Diamond JR, Vahdat LT, et al. Sacituzumab govitecan in previously treated hormone receptor‐positive/HER2‐negative metastatic breast cancer: final results from a phase I/II, single‐arm, basket trial. Ann Oncol. 2020;31(12):1709‐1718. 141. Tagawa ST, Faltas BM, Lam ET, et al. …

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

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… Diamond P. Gronthos S. Peet D.J. Zannettino A.C. The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma Leukemia 2011 25 1533 1542 10.1038/leu.2011.122 21637285 40. Umezu T. Tadokoro H. Azuma K. Yoshizawa S. Ohyashiki K. Ohyashiki J.H. …

Epidemiology, genetics and treatment of multiple myeloma and precursor diseases.

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5-year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapi

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… Blood Cancer J . 2020 ; 10 : 101 . 33057009 10.1038/s41408-020-00367-2 PMC7560599 106 Diamond B , Yellapantula V , Rustad EH , et al. Positive selection as the unifying force for clonal evolution in multiple myeloma . …