Linda Cairns

Recycling existing drugs for cancer therapy: delivering low cost cancer care.

Cancer is one of the leading causes of death today and is only set to worsen as its incidence continues to rise worldwide. The development of novel and effective anti-cancer drugs is a lengthy, extremely costly and inefficient process and many potential compounds are eliminated at the preclinical stages and thereafter many still never make it to the market. The cancer medical community, probably more than any other, understands the urgent need for more effective therapies as the current high cost of cancer care is unsustainable. Drug repurposing or drug repositioning is the application of established drugs to new indications and represents an increasingly promising way to speed up the development of treatments for diseases that do not respond well to standard therapies. The cost of cancer drugs has more than doubled in the past decade. Of the 12 cancer drugs approved in 2012 by the FDA for cancer 11 were priced at more than

Highlights from the ecancer Future Horizons in Lung Cancer conference, 1–2 September 2016: Focusing on the future of treatment for NSCLC and SCLC

100,000 per patient per year. The cost of Gleevec (Imatinib), the enormously profitable Novartis drug for the treatment of chronic myelogenous leukemia, has risen from £18,000 per patient per year to around £21,000 in the UK, and from

Granular cell tumor of the breast: Molecular pathology and clinical management

30,000 to

Highlights of the twelfth annual meeting of the National Cancer Research Institute (NCRI), 6–9 November 2016, Liverpool, UK

92,000 in the US. This is despite the fact that all the research costs were covered by the original price, and the number of patients treated and the length of time they are on the drug have both vastly increased because of the drug’s success. Cheap generic versions are available and will hopefully enter the market as early as 2015 when the main patent on Gleevec expires. In fact the Indian Supreme court overturned a recent attempt by Novartis to extend the patent and block the use of generic versions of Imatinib. Drug repurposing is a strategy with fascinating potential for cutting the cost of cancer care as well as significantly affecting patient outcomes, with two of the most notable examples being Thalidomide and Sildenafil. Thalidomide was commonly used in the late 1950s as a sedative in pregnant women, but was later found to be associated with serious birth defects. Today, it is used to treat multiple myeloma due to its anti-angiogenic activity. Sildenafil (Viagra) was being developed by Pfizer to treat high blood pressure when its ability to ‘treat’ erectile dysfunction was identified as a side-effect, resulting in a complete shift in marketing strategy. Repurposing of approved or abandoned drugs for cancer represents an opportunity to rapidly advance to patients promising drug therapies by capitalizing on existing data and experience. It can take advantage of previous research and development efforts, and detailed information about the drug formulation and safety is usually available, meaning that it can be ready for clinical trials much faster than a brand-new drug. While our understanding of the biology and genetics of cancer has increased dramatically in recent decades, the pace of discovery, development and registration of new drug therapies for cancer has not. Searching for new treatments for cancer among drugs that were already available for other diseases relies on a much greater knowledge of the basic nature behind how these established agents work. This will require new thinking, new approaches, and new collaborations. In fact Cancer Research UK has reached an agreement with AstraZeneca to take an experimental drug, originally designed for asthma, into a clinical trial to treat kidney cancer. In June 2013, the NIH announced funding for nine cooperative agreements between academic research groups with selected industry. The goal is to identify molecules that have already undergone significant research and development by the pharmaceutical industry to more quickly advance new treatments for patients. A recent paper in Cancer Research [1] demonstrated the power of bioinformatics-based drug approaches to rapidly repurpose approved drugs and identified a novel class of molecules, Tricyclic Antidepressants, as Inhibitors of Small Cell Lung Cancer, a cancer for which no effective novel systemic treatments have been identified in several decades. The Repurposing Drugs in Oncology (ReDO) project, an international collaboration between researchers working for not-for-profit patient-centred organisations in Europe and the United States, aims to accelerate the repurposing of non-cancer drugs for new indications in oncology. To do this it aims to identify the most promising candidate drugs; to summarise the often dispersed pre-clinical and clinical data; to explore potential combination therapies with existing anti-cancer or other repurposed drugs; and to work with investigators to develop clinical trials using these combinations. Many of the candidate drugs identified by the ReDO project are low-cost and/or generic drugs that have well-characterized pharmacokinetics and toxicity profiles at clinically relevant doses and have direct clinical evidence of efficacy – often from small trials or from published case reports. Example candidates include mebendazole, nitroglycerin, cimetidine, clarithromycin, diclofenac and itraconazole. ReDO hopes to make known their potential clinical benefit in the treatment of cancer and to bring these drugs to patients as quickly as is possible. Ideally, multiple foundations should support investigator-driven pivotal trials to confirm the efficacy of these products or product combinations.

Ataxia-Telangiectasia patients get a rare chance to meet the experts at a dedicated workshop in IFOM (the FIRC Institute of Molecular Oncology)

The ‘Future Horizons in Lung Cancer’ meeting was designed to bring leading scientists together alongside clinicians to discuss the most recent advances in lung cancer pathophysiology and treatment. The aim was to take those attending the event on a journey through decades of lung cancer research and understanding, with topics spanning from screening and surgical care to “omics” approaches for drug target and biomarker discovery. There were also several talks describing the role of radiotherapy in lung cancer and advancements in imaging techniques, aiding surgeons in their attempts to resect early lesions. Current standards of care were both challenged and celebrated, while new and innovative immunotherapies also came into the spotlight. The meeting, held over two days, attracted a high calibre of speakers and delegates from across the globe. There were 10 sessions in total focusing on the latest therapeutic advances and predictions for the future of lung cancer treatment. Highlights included a key note lecture from Dr Frances Shepherd packing 40 years of lung cancer research into a 40-minute presentation. Heated debates were had regarding the validity of maintenance therapy and immune checkpoint inhibitors that have taken the research community by storm. The latest developments in imaging, surgery, systemic and radiotherapy were presented over 10 sessions of exciting, innovative and stimulating presentations, leaving the audience lively yet pensive.

Cancer immunotherapy: From the lab to clinical applications - Potential impact on cancer centres' organisation

Granular cell tumor is a rare condition that occasionally affects breast parenchyma: approximately, 5%‐15% of all granular cell tumors represent 1:1000 of breast tumors. In this study, we reported a consecutive series of 12 patients with primary granular cell tumor of the breast observed at our institute, focusing attention on preoperative management, surgical approach, and long‐term follow‐up. Eight cases (8/12; 66.78%) presented with left‐breast tumors; in the majority of patients (11/12; 91.7%), the lesion was identified in one of the upper quadrants. Specifically, upper intern quadrants (10 cases) were more affected. Surgical excision was performed in all patients. Mean diameter at pathologic section was 11.4 mm (range: 5‐22). Tumor relapse was reported only in one case (8.3%). Mean follow‐up was 98.1 months (range: 1‐192). We proposed a model to explain the molecular mechanism of granular cell tumorigenesis associating to the high level of S100 protein. Management of primary granular cell tumor of the breast requires a correct initial diagnosis using breast imaging associated with core biopsy. Surgical procedure with wide resection or quadrantectomy requires a careful evaluation of breast margins.

Highlights from the 38th SABCS annual meeting, 8th – 12th December 2015, San Antonio, USA

The annual meeting of the National Cancer Research Institute (NCRI), held in Liverpool, UK, is a multidisciplinary conference. The meeting generally outlines research trends for the coming year and is aimed at cancer professionals at every level. The most important themes discussed for this conference was that of cancer stem cells. Alongside once again prominence was given to topics of cancer evolution and the role of social prevention programmes like previous years.

Conference report from the 2015 OECI Oncology Days, Portugal, 22–24 June—tumour heterogeneity and next generation sequencing: morphology and technology

Ataxia telangiectasia (A-T) is a genetic syndrome characterized by cerebellar degeneration, telangiectasia, immunodeficiency and cancer predisposition. A-T occurs in between 1 in 40,000 and 1 in 100,000 live births. The first symptoms normally occur in early childhood when the infant begins to walk. Affected children have immunodeficiency and an increased predisposition for cancers. A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name.

Twenty years of activity at the European Institute of Oncology, Milan, Italy

This report covers the Immunotherapy sessions of the 2016 Organisation of European Cancer Institutes (OECI) Oncology Days meeting, which was held on 15th–17th June 2016 in Brussels, Belgium. Immunotherapy is a potential cancer treatment that uses an individual’s immune system to fight the tumour. In recent years significant advances have been made in this field in the treatment of several advanced cancers. Cancer immunotherapies include monoclonal antibodies that are designed to attack a very specific part of the cancer cell and immune checkpoint inhibitors which are molecules that stimulate or block the inhibition of the immune system. Other cancer immunotherapies include vaccines and T cell infusions. This report will summarise some of the research that is going on in this field and will give us an update on where we are at present.

Eurocan Platform meeting: European recommendations for biomarker-based chemoprevention trials.

The 2015 San Antonio Breast Cancer Symposium (SABCS) annual meeting highlighted the latest discoveries in breast cancer research and as ever provided a unique opportunity for investigators from all over the world to meet and network. With the rapidly increasing pace of discoveries in the basic, translational, and clinical sciences, mainly because of the advent of new technologies, cancer researchers are making rapid progress that is having significant patient benefit. This year’s meeting featured studies on targeted therapy plus endocrine therapy for metastatic disease with a mutation of PIK3CA, chemotherapy combinations for HER-2-positive disease, long-term outcomes of different surgeries for early-stage cancers, and the first-ever trial of a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor as an adjuvant treatment for breast cancer in postmenopausal women. In the educational session, there was significant emphasis on the role of metabolic syndrome and lifestyle on breast cancer outcome.