The award of this year's Nobel prize in physiology or medicine to Dr Jim Allison and Dr Tasuku Honjo is a defining moment for cancer research that we want to recognize. You'll hear from Dr Allison on the very day he heard the announcement. We also take a closer look at what it takes to be a great scientist and explore the limitations on how many people the Nobel prize can recognize in a given year. If you want to increase your chance of winning, 1993 laureate Sir Richard Roberts FRS takes us through his "Ten Simple Rules to Win a Nobel Prize." We have come full circle in our journey over the last 3.5 years and now hear the results of a "practice changing" phase 3 cancer immunotherapy trial in triple negative breast cancer (TNBC) that we first talked about in the inaugural episode of the podcast, "The Checkpoints Show." There's also an update from the recent ESMO congress on results from a phase 3 ovarian cancer trial that is potentially "life changing" for women with a BRCA mutation.  Scientists and clinical researchers you'll hear on this episode include a rich diversity of viewpoints and perspectives: Sir Richard Roberts FRS, Dr James Allison, Dr Phil Greenberg, Dr Ignacio Melero, Dr Pasi Jänne, Dr Tony Mok, Dr Kathleen Moore, Dr Leisha Emens, Dr Sherene Loi, Dr Peter Schmid, Dr Dan Chen and Dr Ira Mellman. Several of the interviews were recorded at the 2018 CRI CIMT EATI AACR international cancer immunotherapy conference (CICON) in New York, 2018 European Society for Medical Oncology (ESMO) Congress in Munich and the 2018 Society for Immunotherapy of Cancer (SITC) annual meeting in Washington DC. This episode was sponsored by Genentech, we're grateful for their support. You can find more information about this episode and links to additional information in the show notes on https://noveltargets.com © 2018 Blue Ice Publishing LLC. All Rights Reserved

In this episode we continue our journey looking at the innate immune system and focus on some important immune cells called natural killer (NK) cells and their potential in cancer immunotherapy. You'll hear from both academic and industry experts who are active in research in this field, including Dr Todd Fehniger (Washington University in St Louis), Dr Michael Caligiuri (City of Hope), Dr Jeff Miller (Minnesota), Prof Eric Vivier (Innate Pharma via Marseille Immunopole), Dr Nick Huntington (Walter & Eliza Hall Institute in Melbourne), Dr James Gulley (NCI), and Dr Deepak Sampath (Genentech). Some important topics we will cover: - What are NK cells? - What do the do? - How do they 'see'? - How can they be boosted? - What kind of approaches have been developed therapeutically? - What kind of clinical data have we seen so far? - What's the vision for the future of NK cell therapy development? You can find more detailed information about the topics discussed in the show notes on https://noveltargets.com. These interviews were conducted in various cities around the world or at AACR, ASCO, ASH, BMT Tandem and CIMT meetings between 2016 to 2018. Full transcripts of the individual interviews can be found on https://biotechstrategyblog.com (subscription required). The music is by violinist and composer David Schulman. Listen to more at http://www.quietlifemotel.com. © 2018 Blue Ice Publishing LLC. All Rights Reserved

In this episode we explore the innate immune system and find out what it is, what it does and why it matters in both health and disease. You'll hear various perspectives from both academic and industry experts who are active in research in this field, including Dr Glen Barber (Miami), Prof George Coukos (Lausanne), Dr Adi Diab (MD Anderson), Dr Tom Dubensky (Tempest Therapeutics via Aduro Biotech), Dr Tom Gajewski (Chicago), Dr Jonathan Lancaster (Myriad), Dr Ira Mellman (Genentech), Prof Eric Vivier (Innate Pharma via Marseille Immunopole/CIML), Dr Jonathan Zalevsky (Nektar Therapeutics). Some important topics we will cover: - What is the innate immune system? - What does it do? - How is it different from the adaptive immune system? - Is it really separate from the adaptive system? - STING (Stimulator of Interferon Genes) - Biomarkers - Toll-like Receptors (TLRs) You can find more detailed information about the topics discussed in the show notes on https://noveltargets.com. These interviews were conducted in various cities around the world or at AACR, ASCO and SITC meetings between 2016 to 2018. Full transcripts of the individual interviews can be found on https://biotechstrategyblog.com The music is by violinist and composer David Schulman. Listen to more at http://quietlifemotel.com. © 2018 Blue Ice Publishing LLC. All Rights Reserved

In this episode we take a look a look at how cytokines can be employed to modulate the tumour microenvironment in favourable ways. You'll hear various perspectives from numerous academic and industry experts who are active in research in this field, including Dr Mario Sznol (Yale), Dr James Gulley (NCI), Dr Adi Diab (MD Anderson), Dr Jonathan Zalevsky (Nektar Therapeutics), Dr Sanjeev Mariathasan (Genentech), Prof Tom Powles (Barts Cancer Institute), Dr Kunle Odunsi (Roswell Park), and Dr Renier Brentjens (Memorial Sloan Kettering). Some important topics that we will cover: - What are cytokines? - Why do they matter? - The good and bad effects they can induce on the tumour microenvironment (TME) - Interleukins - Transforming Growth Factor beta (TGFβ) - The increasingly important role for reverse translation research in helping to understand what's going on in the TME in order to improve rational future immuno-oncology (IO) combination approaches - Can we determine differences in responders and non-responders? - Novel approaches in clinical development, including CAR T cell therapies in solid tumours, and why they are different from previous approaches that were either too toxic or ineffective You can find more detailed information about the topics discussed in the show notes on https://noveltargets.com. Most of the interviews were conducted at recent AACR and ASCO meetings in 2018 and full transcripts of the individual interviews can be found on https://biotechstrategyblog.com. The music is by violinist and composer David Schulman. Listen to more at http://www.quietlifemotel.com © 2018 Blue Ice Publishing LLC. All Rights Reserved.

Welcome back to Season 4! In this latest episode, we take a look at data from immunotherapy clinical trials from several different angles and investigate the challenges associated presented by different combination partners, control arms, patient populations, biomarkers, line of therapy, etc. When important phase 3 readouts hit the newswires, inevitable questions follow: - Is the data practice changing? - Which regimen should be used with which patient population? - What happens on the Weds after the conference in the clinic when a new patient presents; will oncologists do anything differently? While it's nice to have several positive trial results, how do physicians go about making sense of them? What are some of the hidden pitfalls of cross-trial comparisons that we should watch out for and consider? Professor Tom Powles (Barts Cancer Centre, London) is our narrator for this show and walks us through various challenges and opportunities that both investigators and oncologists face. We explore various examples from recent randomised clinical trial results in lung, renal and bladder cancers, as well as metastatic melanoma.   Along the way, we interview numerous experts who have treated cancer patients with several different types of therapy and participated in clinical trials, including Drs Roy Herbst (Yale), Hossein Borghaei (Fox Chase), Jack West (Swedish), Alan Sandler (Genentech) in lung cancer. Other specialists discuss the underlying science and practical aspects they have experienced to help illustrate the challenges and opportunities that the complexity in unravelling cancer presents and look at how emerging biomarkers can help. These include Professor Charles Swanton FRS and Dr Nicky McGranahan (UCL), Drs David Fabrizio (Foundation Medicine) and Kunle Odunsi (Roswell Park).   We also touch on the future and how important 'big data' is becoming, not just in terms of clinical trials, but the possibilities that it offers for personalising therapy. Dr Lizzie Coker (now at Sanger Institute) explains how her work on developing a public repository is intended to empower basic scientists with big datasets and the value of social media for young researchers. You can find more information in the show notes on https://noveltargets.com © 2018 Blue Ice Publishing LLC. All Rights Reserved.

In this episode we're exploring some controversial issues in cancer research including real world versus clinical trial experience and immune related toxicities, as well as highlighting strength and weaknesses around some encouraging new data with several therapies in development for different hematologic malignancies. Not everything about cancer immunotherapies is positive -- there are challenges associated with this promising approach too. Despite what many people may believe, it's not just about merely tweaking one's immune system and the cancer goes away. Most of the interviews you'll hear were recorded at the 2017 annual meeting of the American Society of Hematology (ASH) in Atlanta. In this episode you'll hear leading experts, including Drs Paul Richardson and Philippe Armande (Dana-Farber), Dr John Leonard (Weill Cornell), Dr Ian Flinn (Sarah Cannon), Dr Nancy Simonian (Syros) and Drs Michael Wenger and Deepak Sampath (Genentech). Some of the topics covered include: * Real world experiences in myeloma and lymphoma * The challenges of combining immune checkpoint blockade with IMiDs * How combining several immunotherapies after allo transplant can be challenging in Hodgkins Lymphoma * A look at progress with two antibody drug conjugates and physician reactions to the data * Emerging targeted therapies combinations and their outlook * Can a BCL-2 inhibitor be safely combined with other approaches in CLL * Perspectives on CAR T cell therapy and their potential competitors In particular, Dr Paul Richardson discusses real world data, tolerability, managing toxicities and some new agents on the horizon that he is excited about. We also hear from Dr John Leonard on his perspectives around several new developments in aggressive lymphomas, including brentuximab vedotin in the ECHELON-1 study and his latest thoughts around CAR T cell therapies in diffuse large cell lymphoma (DLBCL). All in all, there's much to reflect on and think about in the blood cancers and plenty to watch out for in 2018. You can find more information on the Novel Targets website (https://noveltargets.com) along with links to some of the scientific papers mentioned. Copyright © Blue Ice Publishing LLC, 2018. All Rights Reserved.

In this latest episode we're exploring an up and coming area of cancer research, namely therapeutic cancer vaccines. If we want to jumpstart the immune system in cold/non-inflamed/desert tumours, then we need to find ways to attract more T cells into the tumour(s). Cancer vaccines can potentially do that but they have had a bit of a chequered history, with many failures and at least in the US, only one has been approved by the FDA to date. In this show you'll hear from leading cancer immunotherapy experts involved in cancer vaccine research, including Dr Cathy Wu (Dana Farber), Prof Ton Schumacher (Netherlands Cancer Institute), Prof Ugur Sahin (BioNTech and TRON), Prof Kees Melief (Leiden and ISA Pharma), Prof George Coukos (Lausanne), and Dr Ira Mellman (Genentech). Some important topics we cover include: - What's different about the next generation cancer vaccine approaches? - Neoantigen and neoepitope approaches - DNA and RNA vaccines - HPV vaccines - Dendritic cell vaccines - Integration with existing checkpoint blockade approaches In particular, Dr Ira Mellman and Prof Ton Schumacher walk us through the challenges and opportunities associated with identifying and harnessing neoantigen and neoepitopes, and how the current approaches are quite different from what went before. Or put another way -- why they think the latest iterations are more likely to be successful in the clinic! Dr Cathy Wu talks about her work to systematise the identification of neoantigens in a hyper mutated tumour example (melanoma) and a less mutated cancer type (GBM) in order to produce a viable vaccine. We also hear from Prof Ugur Sahin on his RNA vaccine devolopment with neoepitopes and the work they are doing to continually improve the process in melanoma. Alternative approaches in oncology R&D are reviewed by Profs Kees Melief (HPV-positive head and neck cancer) and George Coukos (using dendritic cell vaccines in ovarian cancer). You can find more information on the Novel Targets website (https://noveltargets.com) along with links to some of the scientific papers mentioned in the show.

In this episode we're exploring ways to jumpstart the immune system so that subsequent therapies can be more effective, especially in cold non-inflamed tumours. It is becoming increasingly clear that people with pre-existing immunity respond better to cancer immunotherapies. - What is it, why does it matter and how do we measure it? - What types of therapeutic approaches might be helpful for boosting it? In this show, you'll hear from some new and familiar expert voices alike: - Dr Jérôme Galon (INSERM) discusses the concept of pre-existing immunity and why it matters - Dr Carlos Paya (Immune Design) explains how a cancer testis vaccine can boost immunity in cold tumours such as sarcomas; - Dr Mario Sznol (Yale) talks about cytokines and why they may be an important factor to consider; - Drs Adi Diab (MD Anderson) and Jonathan Zalevsky (Nektar) discuss an immune agonist that may be useful in stimulating key immune cells and act synergistically with checkpoint blockade ; - Drs Friedrich Finckenstein, Dietmar Berger and Dan Chen (Roche Genentech) explain the concept of T cell bispecifics and describe what they found when a novel bispecific was used in a cold tumour such as colon cancer. You can find more information about the topics discussed in the show notes on https://noveltargets.com. All the interviews were first published on https://biotechstrategyblog.com. Copyright © 2017 Blue Ice Publishing LLC. All Rights Reserved.

In the latest episode of Novel Targets, we take a look at new developments in breast cancer. Breast cancer can be organised into several distinct subsets for the purposes of treatment: - Hormone sensitive disease (HR+) - HER2+ - Triple negative breast cancer (TNBC) - Inflammatory breast cancer In addition, physicians also consider risk factors such as tumour size (T), whether the disease has spread to the lymph nodes (N) i.e. negative or positive, and whether there is metastasis (M), which has spread to other parts of the body. This means that lower risk breast cancers include those that are earlier stage, small in size, node negative, no metastasis present or are HR+. In contrast, high risk tumours include those that are larger, have node positive disease, or a HR-. Early stage disease (I-III) is usually reseactable and the aim of treatment is cure. Therapy given prior to surgery is known as neoadjuvant, while that administered after surgery is called adjuvant therapy. Stage IV disease is considered to be unresectable and/or metastatic. In this show, we consider new data across the board with the exception of IBC. Topics of interest include expert reactions from around the world to two important phase III studies recently presented at the ASCO meeting that known as olympiAD (HR- metastatic breast cancer) and APHINITY (HER2+ in the adjuvant setting). We also interviewed thought leaders on new developments with cancer immunotherapies in the neoadjuvant setting and explore what has happened here since we first covered it in the 2nd episode of season 1. Two years on what can we learn? Finally, an important development of relevance to the metastatic setting is the Metastatic Breast Cancer Project run by Dr Nikhil Wagle from the Dana Farber Cancer Institute in Boston. This novel concept involves people with breast cancer from the ground up and curates samples and patient histories so that collaborative research can be undertaken and reported. You can find more information on the Novel Targets website (http://noveltargets.com) along with links to some of the scientific papers that accompany the clinical trial presentations. Copyright © Blue Ice Publishing LLC, 2017. All Rights Reserved.

Welcome back to Season 3. In this episode we're tackling one of the hottest topics in cancer research, why do cancer immunotherapies work in some people, but not in others? Why do they stop working? If we want to obtain long durable responses, then we have to understand and overcome resistance. Most of the interviews you'll hear were recorded at the 2017 annual meeting of the American Association for Cancer Research (AACR) in Washington DC. In this episode you'll hear leading cancer immunotherapy experts including Dr Gordon Mills (MD Anderson Cancer Center), Dr Jason Luke (University of Chicago), Dr Daniel Chen (Genentech), Dr James Gulley (National Cancer Institute), Dr Leisha Emens (Johns Hopkins), Dr Ira Mellman (Genentech), Dr Julie Brahmer (Johns Hopkins), Dr Stephan Grupp (Children's Hospital of Philadelphia) and Dr Christine Brown (City of Hope). Some of the meaty topics covered include: - initial resistance - acquired resistance - immune escape - how we may be able to turn non-responders into responders - overcoming immuno-suppression within the tumor microenvironment. Dr Gulley from the NCI highlights some early yet exciting data on how cancer immunotherapy could be made to work in prostate cancer. We also hear from Dr Christine Brown (pictured) on a novel way to target glioblastoma (GBM) using CAR T cell therapy that offers hope to patients with brain cancer who might otherwise have a dismal prognosis. Cancer immunotherapy is set to become the ultimate personalised medicine, and overcoming resistance will be highly personal too. You can find more information on the Novel Targets website (http://noveltargets.com) along with links to some of the scientific papers mentioned. Copyright © Blue Ice Publishing LLC, 2017. All Rights Reserved.