BioDrugs

Li, Luyuan; Eid, Josiane; Paz, Ana; Trent, Jonathan

doi: 10.1007/s40259-017-0237-2pmid: 28840584

Cellular metabolism reprogramming is an emerging hallmark of cancer, which provides tumor cells with not only necessary energy but also crucial materials to support growth. Exploiting the unique features of cancer metabolism is promising in cancer therapies. The growing interest in this field has led to numerous inhibitors being developed against key molecules in metabolic pathways, though most of them are still in preclinical development. Potential targeted cancer cell metabolic pathways under investigation include glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), glutaminolysis, pentose phosphate pathway (PPP), lipid synthesis, amino acid and nucleotide metabolism. Sarcoma is a type of cancer that arises from transformed cells of mesenchymal origin, in contrast to carcinoma which originates from epithelial cells. Compared with carcinoma, progress towards harnessing the therapeutic potential of targeting sarcoma cell metabolism has been relatively slow. Recently however, with the discovery of cancer-specific mutations in metabolic enzymes such as isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH) in certain sarcoma types, cancer cellular metabolism has been considered more as a source of new targets for treating sarcoma. In this article, we review metabolic enzymes currently tested for cancer therapies and describe the therapeutic potential of targeting IDH mutations and SDH deficiency in sarcomas.

Dean, Katrina; Niven, Robert

doi: 10.1007/s40259-017-0242-5pmid: 28879503

Asthma is increasingly recognised as a heterogeneous group of diseases with similar clinical presentations rather than a singular disease entity. Asthma was historically categorised by clinical symptoms; however, newer methods of subgrouping, describing and categorising the disease have sub-defined asthma. These sub-definitions are intermittently called phenotypes or endotypes, but the real meanings of these words are poorly understood. Novel treatments are currently and increasingly available, partly in the monoclonal antibody environment, and also some physical therapies (bronchial thermoplasty), but additionally small molecules are not far away from clinical practice. Understanding the disease pathogenesis and the mechanism of action more completely may enable identification of treatable traits, biomarkers, mediators and modifiable therapeutic targets. However, there remains a danger that clinicians become preoccupied with the concept of endotypes and biomarkers, ignoring therapies that are hugely effective but have no companion biomarker. This review discusses our understanding of the concept of phenotypes and endotypes in appreciating and managing the heterogeneous condition that is asthma. We consider the role of functional imaging, physiology, blood-, sputum- and breath-based biomarkers and clinical manifestations that could be used to produce a personalised asthma profile, with implications on prognosis, pathophysiology and most importantly specific therapeutic responses. With the advent of increasing numbers of biological therapies and other interventional options such as bronchial thermoplasty, the importance of targeting expensive therapies to patients with the best chance of clinical response has huge health economic importance.

Vakharia, Paras; Silverberg, Jonathan

doi: 10.1007/s40259-017-0241-6pmid: 28853008

Atopic dermatitis (AD) is a complex and heterogeneous inflammatory skin disorder with a profound symptom and lesional burden. Moderate-to-severe AD is particularly challenging to manage, as topical treatments are often inadequate and the systemic immunosuppressants are limited by concerns of toxicity and tolerability. Recent AD research has elucidated the mechanisms and immunologic factors involved in AD pathogenesis. These breakthroughs have led to the development of multiple therapeutic monoclonal antibodies that are directed against specific immunologic targets. This review provides an overview on the pathogenesis of AD as well as the rationale for the targets of various monoclonal antibodies. Additionally, this review explores the efficacy and safety of use for various monoclonal antibodies in the management of AD, as well as the potential role of these agents in the treatment of AD.

Lawrence, Paul; Ceccoli, Joseph

doi: 10.1007/s40259-017-0243-4pmid: 28875300

The advent of RNA interference (RNAi) technology has profoundly impacted molecular biology research and medicine but has also advanced the field of skin care. Both effector molecules of RNAi, short-interfering RNA molecules and microRNAs (miRNAs), have been explored for their relative impact and utility for treating a variety of skin conditions. These post-transcriptional RNA regulatory molecules down-modulate protein expression through targeting of the 3′ untranslated regions of messenger RNAs, leading to their degradation or repression through sequestration. As researchers hunt for genetic linkages to skin diseases, miRNA regulators have emerged as key players in the biology of keratinocytes, fibroblasts, melanocytes, and other cells of the skin. Herein, we attempt to coalesce the current efforts to combat various skin disorders and diseases through the development of miRNA-based technologies.

Aladul, Mohammed; Fitzpatrick, Raymond; Chapman, Stephen

doi: 10.1007/s40259-017-0238-1pmid: 28752242

van Overbeeke, Eline; De Beleyr, Birgit; de Hoon, Jan; Westhovens, Rene; Huys, Isabelle

doi: 10.1007/s40259-017-0244-3pmid: 28929342

Lamb, Yvette; Scott, Lesley; Deeks, Emma

doi: 10.1007/s40259-017-0240-7pmid: 28803431

SB2 is a biosimilar of the reference anti-TNF-α antibody infliximab. In May 2015, it was approved in the EU for use in all indications for which reference infliximab is approved, including rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriatic arthritis and psoriasis. It is also approved in these indications in several other countries, including Korea, the USA and Australia. Characterization of SB2 in preclinical studies showed that it is similar to reference infliximab. SB2 demonstrated pharmacokinetic biosimilarity to reference infliximab in healthy volunteers, and clinically equivalent efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. SB2 was generally well tolerated; the safety and immunogenicity profiles were similar to those of reference infliximab with no additional safety concerns identified. Switching from reference infliximab to SB2 did not impact clinical efficacy, safety or immunogenicity. The role of reference infliximab in the management of autoimmune inflammatory conditions is well established, and SB2 provides an effective biosimilar alternative for patients requiring infliximab therapy.

Blair, Hannah

doi: 10.1007/s40259-017-0245-2pmid: 28921160

GP2013 is the second biosimilar of the reference monoclonal anti-CD20 antibody rituximab to be approved in the EU. It is approved for use in all indications for which reference rituximab is approved, including follicular lymphoma (FL), diffuse large B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis. GP2013 has similar physicochemical and pharmacodynamic properties to those of reference rituximab, and the pharmacokinetic biosimilarity of the agents has been shown in patients with RA. GP2013 demonstrated clinical efficacy equivalent to that of reference rituximab in patients with FL, and was generally well tolerated in this population. The tolerability, immunogenicity and safety profiles of GP2013 were similar to those of reference rituximab. The role of reference rituximab in the management of cancers and autoimmune conditions is well established and GP2013 provides an effective biosimilar alternative for patients requiring rituximab therapy.