Pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma.
Authors: Chamberlain FE, Wilding C, Jones RL, Huang P Abstract 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. Several phase II and III studies of oral TKIs in soft tissue sar...
Source: Expert Opinion on Investigational Drugs - April 24, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Targeting transcription factors in multiple myeloma: evolving therapeutic strategies.
Authors: Li S, Vallet S, Sacco A, Roccaro A, Lentzsch S, Podar K Abstract INTRODUCTION: Transcription factors (TFs) are convergence points of signaling cascades that coordinate cell differentiation, proliferation, survival, and migration; and are commonly deregulated in solid and hematologic malignancies, including multiple myeloma (MM). Several recent studies indicate that the inhibition of TFs may lead to selective tumor cell death with little or no consequences for normal cells due to redundancy in signaling pathways. Nuclear hormone receptor (NHR)- TFs belong to the most common therapies in oncology today. In c...
Source: Expert Opinion on Investigational Drugs - April 10, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

An update on recent developments in the search for hepatitis C virus therapies with pan-genotypic efficacy.
Authors: Borgia G, Scotto R, Buonomo AR Abstract INTRODUCTION: Pangenotypic drugs against HCV infections led to high rates of virologic response with very limited adverse events. Moreover, they are easy to administer among all HCV genotypes with minimal changes in treatment schedule. For this reason, the demand for new antivirals is greatly lowered. Areas covered. We discuss results from trials assessing safety and efficacy of Ravidasvir, which is the only direct-acting antiviral currently in clinical development. Expert opinion. The currently available pangenotypic drug combinations are very effective in HCV eradi...
Source: Expert Opinion on Investigational Drugs - April 6, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Dasatinib as an investigational drug for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults.
Authors: Brattås MK, Reikvam H, Tvedt THA, Bruserud Ø Abstract INTRODUCTION: Acute lymphoblastic leukemia (ALL) with BCR-ABL1 translocation is an aggressive malignancy that is usually treated with intensive chemotherapy with the possibility of allogeneic stem cell transplantation. The encoded fusion protein may be important for leukemogenesis; clinical studies show that dasatinib has an antileukemic effect in combination with steroids alone or intensive chemotherapy. Areas covered. Relevant publications were identified through literature searches (the used terms being acute lymphoblastic leukemia plus ...
Source: Expert Opinion on Investigational Drugs - March 28, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders.
This article covers the mechanism of action, pharmacology and clinical trial results of ixazomib while under investigation for the treatment of various lymphoproliferative disorders. We examine the findings from several phase 3 clinical trials (i) the pivotal TOURMALINE-MM1 study investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone (ii) the TOURMALINE-MM3 study investigating ixazomib versus placebo as a maintenance therapy in newly-diagnosed MM following induction therapy and autologous stem cell transplantation,(iii) the TOURMALINE-MM2 study investigating ixazomib versus placebo in comb...
Source: Expert Opinion on Investigational Drugs - March 27, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Clinical profile of the functionally selective glucocorticoid receptor agonist BI 653048 in healthy male subjects.
Conclusion BI 653048 demonstrated the desired anti-inflammatory effects of the nonsteroidal GC; however, the undesirable side-effect profile associated with GC steroids could not be disassociated from BI 653048. PMID: 30908082 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - March 27, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Triple-drug chemotherapy regimens in combination with an anti-EGFR agent in metastatic colorectal cancer - prospects from phase II clinical trials.
We describe the overall safety and tolerability profiles based on a literature review of all published phase I and II clinical trials in this setting. Drug exposure, tumour mutational status and metastases resectability are discussed. A review of pubmed and abstracts of major oncology congresses from 2009 to 2018, with MeSH and full-text search terms for clinical trials of anti-EGFR for "metastatic" or "advanced" "colorectal cancer/adenocarcinoma" was implemented. Only English language publications were included. Expert opinion: Efficacy data from phase II trials are promising, but the safety ...
Source: Expert Opinion on Investigational Drugs - March 25, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Genomics in non-adenoid cystic group of salivary gland cancers: one or more druggable entities?
We describe the pattern of potentially targetable genomic alterations in non-ACC salivary gland malignancies according to their frequency rather than to the single non-ACC histotype Expert Opinion/Commentary: The genetic profiling through in-depth molecular analyses [e.g. Next-generation sequencing (NGS)] is advised in all patients affected by recurrent and/or metastatic non-ACC SGCs to find any potentially druggable target. Some histotypes may carry driving mutations (e.g. salivary duct carcinoma and AR expression) that must be investigated and defined. For the rare cancers, access to a referral center is recommended to o...
Source: Expert Opinion on Investigational Drugs - March 24, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

RX-3117 (fluorocyclopentenyl cytosine): a novel specific antimetabolite for selective cancer treatment.
Authors: Balboni B, El Hassouni B, Honeywell RJ, Sarkisjan D, Giovannetti E, Poore J, Heaton C, Peterson C, Benaim E, Lee YB, Kim DJ, Peters GJ Abstract INTRODUCTION: RX-3117 is an oral, small molecule cytidine analog anticancer agent with an improved pharmacological profile relative to gemcitabine and other nucleoside analogs. The agent has excellent activity against various cancer cell lines and xenografts including gemcitabine-resistant variants and it has excellent oral bioavailability; it is not a substrate for the degradation enzyme cytidine deaminase. RX-3117 is being evaluated at a daily oral schedule of 70...
Source: Expert Opinion on Investigational Drugs - March 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Expert opinion on interleukin-12/23 and interleukin-23 antagonists as potential therapeutic options for the treatment of inflammatory bowel disease.
Authors: Wong U, Cross RK Abstract INTRODUCTION: Blockade of interleukin (IL)-12 and IL-23 is a novel therapeutic target for inflammatory bowel disease (IBD). The monoclonal antibody targeting the shared p40 subunit of IL-12 and IL23, namely ustekinumab, has been approved for Crohn's disease (CD) and has demonstrated promising results in treatment of ulcerative colitis. Several agents targeting the IL-23-specific p19 subunit are currently in various stages of development. These newer agents have the potential to provide safety benefits. Areas covered: This review discusses the current state of IL-12/23 and IL-23 an...
Source: Expert Opinion on Investigational Drugs - March 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Using DDP-4 inhibitors to modulate beta cell function in type 1 diabetes and in the treatment of Diabetic Kidney Disease.
Authors: Davis H, Jones Briscoe V, Dumbadze S, Davis SN Abstract INTRODUCTION: DPP-4 inhibitors have pleomorphic effects that extend beyond the anti-hyperglycemic labeled use of the drug. DPP-4 inhibitors have demonstrated promising renal protective effects in T2DM and T1DM and protective effects against immune destruction of pancreatic beta-cells in T1DM. Areas Covered: The efficacy of DPP-4 inhibitors in the treatment of diabetic kidney disease and possible adjunct with insulin in the treatment of T1DM to preserve beta-cell function. Pertinent literature was identified through Medline, PubMed and ClinicalTrials.g...
Source: Expert Opinion on Investigational Drugs - March 10, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Therapy of acute myeloid leukemia: therapeutic targeting of tyrosine kinases.
Authors: Cioccio J, Claxton D Abstract INTRODUCTION: Tyrosine kinases (TKs) drive cell survival and proliferation in many normal and malignant cell types. TKs are frequently mutated in acute myeloid leukemia (AML) and hence are increasingly targeted. The management of AML has dramatically improved because of TKI-targeted treatment. Areas Covered: This review provides a biological background for TK inhibitors (TKIs) in AML and reviews their use in the clinic. TK expression and mutation in AML are explored with a focus on TKs associated with specific AML subsets and treatment outcomes. TKIs that specifically target F...
Source: Expert Opinion on Investigational Drugs - February 19, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Ridinilazole for the treatment of Clostridioides difficile infection.
This article covers the chemistry, mechanism of action, in vitro microbiology versus C. difficile and host microbiota, pre-clinical and clinical efficacy, pharmacokinetics, pharmacodynamics and safety and tolerability of ridinilazole. Expert opinion: Ridinilazole is a novel antibiotic with ideal properties for the treatment of CDI. Given the promising results from the phase II clinical trial, ridinilazole may have the capability to lower the risk for CDI recurrence thus improving sustained clinical response rates - a current unmet medical need. Assuming a positive phase III trial, ridinilazole will enter a market with heig...
Source: Expert Opinion on Investigational Drugs - February 17, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Do investigational MET inhibitors have potential for the treatment of gastric cancer?
Authors: Athauda A, Chau I PMID: 30768360 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - February 17, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Emerging patient-specific treatment modalities in head and neck cancer - a systematic review.
Authors: Elicin O, Cihoric N, Vlaskou Badra E, Ozsahin M Abstract INTRODUCTION: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates heterogeneous molecular characteristics and features of tumor-host interaction. Beside radiotherapy and surgery, the current standard of care in systemic treatment involves the use of cytotoxic chemotherapy, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). There are also other modalities being developed under the category of immunotherapy, but they are overshadowed by the recent advancements of immune checkpoint inhibitors. Areas Covered: Thi...
Source: Expert Opinion on Investigational Drugs - February 15, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Experimental therapies targeting apolipoprotein C-III for the treatment of hyperlipidemia - spotlight on volanesorsen.
Authors: Milonas D, Tziomalos K Abstract INTRODUCTION: Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides (TG). Apolipoprotein C3 (APOC3) is a key regulator of TG metabolism and its targeting may reduce TG levels and cardiovascular risk. Areas covered: We discuss APOC3-targeted experimental treatments for dysli...
Source: Expert Opinion on Investigational Drugs - February 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drug therapies currently in early stage clinical development for the treatment of clostridioides (clostridium) difficile infection.
Authors: Tran MN, Kullar R, Goldstein EJ Abstract INTRODUCTION: Clostridioides (Clostridium) difficile Infection (CDI) is an urgent global threat causing ~500,000 infections annually in the United States of America (USA) and is associated with a 36% 30-day attributable mortality rate. Despite the availability of three therapeutic agents, CDI recurrence occurs in 20-40% of patients, with a 30-40% second recurrence rate in these patients. Consequently, there is a need for novel agents for treating CDI. Areas covered: We searched MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, ...
Source: Expert Opinion on Investigational Drugs - February 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational multitargeted kinase inhibitors in development for head and neck neoplasms.
Authors: Sola AM, Johnson DE, Grandis JR Abstract INTRODUCTION: Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) survival rates remain stagnant. Current treatment is associated with significant toxicities and includes chemotherapy, radiation, surgery and few targeted treatments. Targeted treatments, epidermal growth factor receptor (EGFR)-targeted agent, cetuximab, and immune checkpoint inhibitors, pembrolizumab and nivolumab, show improved toxicity profiles and modestly improved survival in select patients. An urgent need remains to identify novel targeted treatments for single-agent or...
Source: Expert Opinion on Investigational Drugs - February 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Experimental and investigational phosphodiesterase inhibitors in development for asthma.
Authors: Ntontsi P, Detta A, Bakakos P, Loukides S, Hillas G Abstract INTRODUCTION: Severe, inadequately-controlled asthma remains a clinical challenge. For this reason, clinical trials and preclinical experimental studies on novel agents as an add-on therapies continue emerge. Phosphodiesterases (PDEs) are enzymes that regulate the function of immune cells by hydrolyzing cyclic guanosine monophosphate/cGMP and cyclic adenosine monophosphate/cAMP. PDEs are divided into subfamilies [PDE3, PDE4, PDE5 and PDE7] which are mainly found in the respiratory tract. Inhibitors of PDEs have already been approved for COPD and ...
Source: Expert Opinion on Investigational Drugs - January 28, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Early clinical trials of Toca 511 and Toca FC show a promising novel treatment for recurrent malignant glioma.
Authors: Philbrick BD, Adamson DC Abstract INTRODUCTION: Glioblastoma and anaplastic astrocytoma are two of the most aggressive and common glioma malignancies in adults. These high-grade gliomas (HGG) universally recur despite aggressive treatment modalities and have a median overall survival (mOS) of approximately 14 months from initial diagnosis. Upon recurrence, there is no standard of care and these patients have a dismal prognosis of around 9 months at time of recurrence. Areas covered: In this article, we assess the newly published phase I data of Toca 511 and Toca FC, a two-drug combination therapy for recur...
Source: Expert Opinion on Investigational Drugs - January 26, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

New drugs in early-stage clinical trials for allergic rhinitis.
Authors: Heffler E, Brussino L, Del Giacco S, Paoletti G, Minciullo PL, Varricchi G, Scadding G, Malvezzi L, De Virgilio A, Spriano G, Puggioni F, Fornero M, Rolla G, Canonica GW Abstract INTRODUCTION: Allergic rhinitis (AR) is the most common allergic disease, and it has a relevant impact on the quality of life of the patient. Treatment of AR includes a combination of strategies of proven efficacy and effectiveness; however, a relevant proportion of patients remain uncontrolled. Areas covered: This review article summarizes emerging therapeutic approaches to AR; these approaches include nasal sprays, oral dru...
Source: Expert Opinion on Investigational Drugs - January 26, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Oral investigational drugs currently in phase I or phase II for the amelioration of menopausal symptoms.
Authors: Genazzani AR, Gaspard U, Foidart JM Abstract INTRODUCTION: Menopausal symptoms have a substantial effect on the quality of life of many women, hence investigations for the amelioration of menopausal symptoms continue to be necessary. The two main approaches to the amelioration of symptoms are hormone therapy (HT) and non-hormonal therapy. Areas covered: This review provides a background for understanding the types of menopausal symptoms and their underlying physiology. The early clinical development of a natural estrogen (estetrol, E4), neurokinin 3 receptor (NK3R) antagonists and other non-hormonal therap...
Source: Expert Opinion on Investigational Drugs - January 26, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Costimulatory pathway targets for autoimmune and inflammatory conditions: clinical successes, failures, and hope for the future.
Authors: Spicer P, Runkel L PMID: 30661473 [PubMed - in process] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 23, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Correction.
Authors: PMID: 30646767 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 18, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational luteinizing hormone releasing hormone (LHRH) agonists and other hormonal agents in early stage clinical trials for prostate cancer.
Authors: Singla N, Ghandour RA, Raj GV Abstract INTRODUCTION: The treatment and management of prostate cancer continues to evolve; newer classes of agents and combination therapies are being developed and some are being investigated in early phase clinical trials. Areas covered: We discuss investigational hormonal agents for the treatment of prostate cancer and focus primarily on luteinizing hormone releasing hormone (LHRH) agonists in early stage trials. We look at agents that target the hormonal axis, including anti-androgens, gonadotropins, estrogenic agents and progestogenic agents and other non-hormonal agents...
Source: Expert Opinion on Investigational Drugs - January 18, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

New drugs under investigation for the treatment of alopecias.
Authors: Ocampo-Garza J, Griggs J, Tosti A Abstract INTRODUCTION: Alopecia is a very common complaint in medical practice, which usually has a large psychological impact in patients. Treatment of alopecia is often difficult and frustrating for patients and clinicians owing to the slow growth rate of the hair, long treatment terms, limited efficacy and possible adverse side effects. Areas covered: This paper reviews the new and emerging treatments for two of the most common forms of alopecia, known as androgenetic alopecia and alopecia areata. A literature search of PubMed/MEDLINE and ClinicalTrial.gov was performed...
Source: Expert Opinion on Investigational Drugs - January 16, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Rapastinel - an investigational NMDA-R modulator for major depressive disorder: evidence to date.
Authors: Ragguett RM, Rong C, Kratiuk K, McIntyre RS Abstract INTRODUCTION: Major depressive disorder (MDD) is a debilitating disorder with increasing prevalence globally. Despite the development of novel treatments for MDD, many patients present with treatment resistant depression (TRD), identified by treatment non-response following one or more adequate trials of an antidepressant. Rapastinel may prove to be a viable treatment for TRD; it has the potential to produce a rapid antidepressant response without serious adverse events and improve functional symptoms. Areas covered: We review the efficacy of rapastinel ...
Source: Expert Opinion on Investigational Drugs - December 27, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs for the treatment of acute myocardial infarction: focus on antiplatelet and anticoagulant agents.
Authors: Yandrapalli S, Andries G, Gupta S, Dajani AR, Aronow WS Abstract BACKGROUND: Advances in our understanding of the complex pathophysiologic mechanisms responsible for high-risk atherosclerotic plaque rupture resulting in acute myocardial infarction (AMI) have led to the development of numerous antiplatelet and anticoagulant agents for treatment of AMI. Areas covered: We review various antithrombotic drugs which were recently investigated for the treatment of AMI. A MEDLINE search for relevant articles on newer antiplatelet agents and anticoagulants drugs for the treatment of AMI was performed, and important...
Source: Expert Opinion on Investigational Drugs - December 26, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Emerging oral VEGF inhibitors for the treatment of renal cell carcinoma.
Authors: Stitzlein L, Rao P, Dudley R Abstract INTRODUCTION: The incidence of renal cell carcinoma (RCC) has increased in recent years and, unfortunately, many patients initially present with metastatic disease. When surgery is not an option, treatment involves administration of targeted therapies. The vascular endothelial growth factor (VEGF) pathway has been identified as an important mediator for the development of RCC. Numerous agents target VEGF-mediated signaling, yet resistance and progressive disease still persists. Novel small molecule VEGF inhibitors with high affinity for the VEGF receptor (VEGFR) have b...
Source: Expert Opinion on Investigational Drugs - December 24, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cannabis for cancer - illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology.
Authors: Turgeman I, Bar-Sela G Abstract INTRODUCTION: A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes. Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines. Areas covered: The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids were classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products...
Source: Expert Opinion on Investigational Drugs - December 24, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational PI3K/AKT/mTOR inhibitors in development for endometrial cancer.
Authors: Barra F, Evangelisti G, Ferro Desideri L, Di Domenico S, Ferraioli D, Vellone VG, De Cian F, Ferrero S Abstract INTRODUCTION: Endometrial cancer (EC) is the most common neoplasm of the female genital tract in developed countries. Despite the progress in early detection and treatment, a significant number of cases of advanced ECs are still diagnosed. These patients have few treatment options and a poor prognosis. Our understanding of EC pathogenesis and progression has been enhanced by recent genomic studies. Among the relevant biological pathways, phosphatidylinositol 3-kinase/AKT (PIK3/AKT)-mammalian targ...
Source: Expert Opinion on Investigational Drugs - December 24, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

AQ-13 - an investigational antimalarial drug.
Authors: Mengue JB, Held J, Kreidenweiss A Abstract INTRODUCTION: AQ-13 is a drug candidate in development for the treatment of p. falciparum infections. The chemical structure is similar to chloroquine, a 4-aminoquinoline, with a shorter diaminoalkane side chain. Chloroquine has been the standard of care for P. falciparum malaria for more than 40 years but the spread of resistant parasites in all malaria endemic regions has led to abandonment of the drug. The outstanding attribute of AQ-13 is its retrieval of activity against chloroquine resistant P. falciparum. Areas covered: We review preclinical and clinical st...
Source: Expert Opinion on Investigational Drugs - December 24, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

CTLA4 antagonists in phase I and phase II clinical trials, current status and future perspectives for cancer therapy.
Authors: Pawlik A, Machaj F, Rosik J, Szostak B Abstract INTRODUCTION: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects. Areas covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with oth...
Source: Expert Opinion on Investigational Drugs - December 24, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

BRAF kinase inhibitors for treatment of melanoma: developments from early-stage animal studies to Phase II clinical trials.
Authors: Fujimura T, Hidaka T, Kambayashi Y, Aiba S Abstract INTRODUCTION: Approximately, 30.4-66.0% of cutaneous melanomas possess a mutation in the BRAF gene that activates downstream signaling through the mitogen-activated protein (MAP) kinase pathway; this provides an attractive target for the treatment of advanced melanoma. Although BRAF inhibitors rapidly suppress melanoma growth, median progression-free survival remains unsatisfactory. Recent clinical trials have investigated drugs that can optimally enhance and prolong the anti-melanoma effects of BRAF inhibitors. Area covered: This review discusses the dev...
Source: Expert Opinion on Investigational Drugs - December 19, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Therapeutic Trends in Pancreatic ductal adenocarcinoma (PDAC).
We describe major advances in the cellular and molecular subtypes based on next generation sequencing and their predictive and prognostic value in PDAC patients. We review aberrant genes involving in defined cellular processes in PDAC. Finally, the current state of drug development with novel investigational agents targeting cell fate, cell survival, genomic instability, tumor-stroma and immune checkpoints are discussed. Expert Opinion: Molecular techniques have revealed distinct driver mutations in PDAC. Common genes and cellular processes are dysregulated in the pathogenesis of PDAC. These cellular processes categorized ...
Source: Expert Opinion on Investigational Drugs - December 14, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

New drugs in preclinical and early stage clinical development in the treatment of heart failure.
Authors: Tamargo J, Caballero R, Delpón E Abstract INTRODUCTION: Heart failure (HF) represents a major health problem because of its high prevalence, high rates of hospitalizations, and mortality and significant healthcare costs. HF comprises a heterogeneous group of syndromes with different pathophysiology, clinical presentations, and response to therapy. Basic research has identified multiple putative therapeutic targets involved in the pathogenesis of HF and many promising drugs are under development. Areas covered: This review summarizes the main drugs currently in preclinical and clinical development fo...
Source: Expert Opinion on Investigational Drugs - December 14, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

New developments in investigational HDAC inhibitors for the potential multimodal treatment of cachexia.
Authors: Penna F, Costelli P Abstract INTRODUCTION: Cachexia is a frequent feature of chronic diseases. This syndrome includes loss of body weight, depletion of skeletal muscle mass and altered metabolic homeostasis. Acceleration of protein and energy metabolism, impaired myogenesis and systemic inflammation contribute to cachexia. Its occurrence impinges on treatment tolerance and on the quality of life of the patient, however, no effective therapy is available yet. Areas covered: This review focuses on the use of histone deacetylase inhibitors as pharmacological tools to prevent or delay cachexia, with reference ...
Source: Expert Opinion on Investigational Drugs - December 13, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Sacituzumab for the treatment of triple-negative breast cancer: is this the poster child of future therapy?
Authors: Zangardi ML, Spring LM, Nagayama A, Bardia A Abstract INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately impacts younger women and is associated with a poor prognosis. Systemic treatment options for metastatic TNBC (mTNBC) are limited to successive lines of cytotoxic chemotherapy agents with low response rates. Trop-2 has been identified as a potential target in epithelial cancers such as TNBC; this has encouraged the development of sacituzumab govitecan (IMMU-132), an anti-Trop-2 antibody-drug conjugate (ADC). Areas covered: We summarize th...
Source: Expert Opinion on Investigational Drugs - December 7, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

An update of cyclooxygenase (COX)-inhibitors in epilepsy disorders.
Authors: Dhir A Abstract INTRODUCTION: Neuroinflammation has a critical role in brain disorders. Cyclooxygenase (COX) is one of the principal drug targets for the reduction of neuroinflammation; however, studies have yielded mixed results for COX-inhibitors in the treatment of diverse acute and chronic models of epilepsy. Areas covered: The article covers the effects of COX-inhibitors in epilepsy disorders. A considerable emphasis has been placed on the antiepileptic and "disease-modifying" properties of COX-1 and COX-2 inhibitors in various preclinical epilepsy models. Expert opinion: The effect of COX-i...
Source: Expert Opinion on Investigational Drugs - December 7, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Therapeutic targets and early stage clinical trials for pulmonary fibrosis.
Authors: Sato S, Yanagihara T, Kolb MR Abstract INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an age-associated, progressive and irreversible fatal interstitial lung disease. Although many drugs have failed in clinical trials, these failures improved the understanding of the pathogenesis of IPF. Currently, there are two drugs approved for IPF that slow the progression of the disease. However, the prognosis for patients with IPF remains poor and the search continues for drugs that inhibit the pathogenic pathways active in IPF to further reduce or even halt the progression of the disease. Areas covered: We hig...
Source: Expert Opinion on Investigational Drugs - December 6, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational therapies in phase II clinical trials for the treatment of soft tissue sarcoma.
This article reviews the most relevant phase II studies that utilize chemotherapy agents (aldoxorubicin, amrubicin, trabectedin alone or in combination with doxorubicin, and gemcitabine plus docetaxel), targeted therapies (Imatinib, dasatinib, regorafenib, tivozanib, palbociclib and selinexor), a combination of chemotherapy plus targeted therapies (fucusing on doxorubicin plus olaratumab) and immunotherapies (pembrolizumab, combination of nivolumab plus ipilimumab and adaptive cell therapy) in STS (other than gastrointestinal stromal tumors) (GIST) published from 2015. Some of these strategies are under further clinical de...
Source: Expert Opinion on Investigational Drugs - December 6, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

HER2-targeted therapy: an emerging strategy in advanced colorectal cancer.
Authors: La Salvia A, Lopez-Gomez V, Garcia-Carbonero R Abstract INTRODUCTION: Colorectal cancer (CRC) is one of the most common malignant tumors; it is a focus of research globally, but the identification of clinically actionable oncogenic drivers remains elusive. HER2 activation is present in approximately 5% of CRC and has acquired resistance to EGFR-targeted therapy. Early clinical trials suggest an emerging role for personalized HER2-targeted therapy in a subset of metastatic CRC. Areas covered: This manuscript reviews the relevance of HER2 activation in CRC and its potential role as a target for therapy. A li...
Source: Expert Opinion on Investigational Drugs - December 6, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Prostaglandin D2 receptor antagonists in allergic disorders: safety, efficacy and future perspectives.
Authors: Marone G, Galdiero MR, Pecoraro A, Pucino V, Criscuolo G, Triassi M, Varricchi G Abstract INTRODUCTION: Prostaglandin D2 (PGD2) is a major cyclooxygenase mediator that is synthesized by activated human mast cells and other immune cells. The biological effects of PGD2 are mediated by D-prostanoid (DP1), DP2 (CRTH2) and thromboxane prostanoid (TP) receptors that are expressed on several immune and non-immune cells involved in allergic inflammation. PGD2 exerts various proinflammatory effects relevant to the pathophysiology of allergic disorders. Several selective, orally active, DP2 receptor antagonists and ...
Source: Expert Opinion on Investigational Drugs - December 6, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Triple GLP-1/GIP/glucagon receptor agonists, a potential novel treatment strategy in Alzheimer's disease.
Authors: Camins A, Ettcheto M, Busquets O, Manzine PR, Castro-Torres RD, Beas-Zarate C, Verdaguer E, Sureda FX, Bulló M, Olloquequi J, Auladell C, Folch J PMID: 30480461 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - November 29, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Atezolizumab for the treatment of triple-negative breast cancer.
Authors: Heimes AS, Schmidt M Abstract INTRODUCTION: Triple-negative breast cancer (TNBC) is associated with poor prognosis and limited treatment options. However, TNBC is known to be more immunogenic compared to other breast cancer subtypes, with tumor-infiltrating lymphocytes (TILs) playing an important prognostic and predictive role. Furthermore, TNBC has a higher level of programmed cell death-ligand 1 (PD-L1) expression. Therapeutic blockade of PD-L1 using atezolizumab is thus expected to activate and enhance tumor-speciļ¬c T-cell responses, resulting in improved antitumor activity. Areas covered: This review...
Source: Expert Opinion on Investigational Drugs - November 27, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Spotlight on Bortezomib: Potential in the Treatment of Hepatocellular Carcinoma.
This study reviews the evidence for the use of Bortezomib (BZB), a first-in-class proteasome inhibitor in advanced Hepatocellular carcinoma (HCC). This review aims to delineate the role of BZB within the management of non-surgical and metastatic HCC, either as an alternative or as an adjunct to the current treatment paradigm. Areas covered: In addition to BZB pharmacology and mechanism of action, safety and tolerance profiles of the drug obtained from clinical trials are explored. The utility of BZB as a therapeutic agent either alone or in combination with other therapies against HCC, including its application in both pre...
Source: Expert Opinion on Investigational Drugs - November 27, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The Jakinibs in systemic lupus erythematosus: progress and prospects.
This article reviews the preliminary data concerning the efficacy of the JAK inhibitors (Jakinibs) in SLE. JAK inhibition has shown promise in murine lupus dermatitis and nephritis. Ex-vivo studies of human SLE have demonstrated the effect of JAK1/2 inhibition on the activation of the STAT proteins and autoantibody production from B cells. A phase II trial reported modest efficacy of baricitinib in improving synovitis in SLE patients. Expert opinions: Inhibition of the JAK-STAT pathway is an attractive therapeutic option. The convenience of oral administration and lower production cost of the Jakinibs could replace the bio...
Source: Expert Opinion on Investigational Drugs - November 23, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Incretin-based therapy for diabetic ulcers: from bench to bedside.
Authors: Ku HC, Liang YJ Abstract INTRODUCTION: Diabetic foot ulcers are a serious complication of diabetes and are associated with pain, disability and poor quality of life. Incretin-based therapy is available for type-2 diabetes. Aside from glucose control, such treatment can impart numerous beneficial effects. Areas covered: This review summarizes the preclinical and clinical evidence supporting incretin-based treatment approaches for diabetic ulcers. Expert opinion: Incretin-based therapy may have a role in the treatment of diabetic foot ulcers; the benefits of such treatment arise from attenuation of inflammat...
Source: Expert Opinion on Investigational Drugs - November 20, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs for the treatment of Zika virus infection: a preclinical and clinical update.
Authors: Han Y, Mesplède T Abstract INTRODUCTION: The Zika virus (ZIKV) infection results in severe neurological complications and has emerged as a threat to public health worldwide. No drugs or vaccines are available for use in the clinic and the need for novel and effective therapeutic agents is urgent. Areas covered: This review describes the latest progress of antiviral development for the treatment of ZIKV infection; it primarily focuses on the literature describing twenty potential anti-ZIKV drugs/agents currently being tested in vivo or in clinical trials. The paper also discusses the need for novel Z...
Source: Expert Opinion on Investigational Drugs - November 17, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Novel drugs for the treatment of chronic pruritus.
Authors: Pereira M, Ständer S Abstract INTRODUCTION: Chronic pruritus (CP) is a multidimensional condition severely affecting the quality of life of those affected. Although a multitude of topical and systemic agents are recommended for CP of different origins, the condition often remains refractory to treatment. However, a deeper understanding of the pathophysiology of CP is leading to the development of novel antipruritic drugs. Areas covered: This paper reviews antipruritic therapies in development by gathering data from recently published articles and clinical trials databases. Interleukin-31 antibodies an...
Source: Expert Opinion on Investigational Drugs - November 16, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research