Personalized therapy in oncology

After the 16th edition held in 2021 in digital format, a new edition of the IBSA Foundation Special Forum, entitled "Personalized therapy in oncology" took place on 16 June 2023 in the auditorium of the Università della Svizzera italiana (USI) as part of the programme of the 17th International Conference on Malignant Lymphoma (ICML). 

The ICML is one of the most important international events in the field of lymphoid neoplasm research and treatment, organised by Professor Cavalli and the Foundation for the Institute of Oncology Research (IOR), in cooperation with the American Association for Cancer Research (AACR) and in collaboration with the European School of Oncology (ESO).

Oncological research is making great strides

Until a few years ago tumors originating from the same type of cells were considered and treated as if they were the same disease, today thanks to the interdisciplinary work of doctors and to techniques that allow increasingly detailed resolution, we know that cancer is a highly dynamic disease with a high degree of heterogeneity not only at the intra-tumor level but also between patient and patient.

At the same time, the ever more complete characterization of recurrent DNA alterations in cancer patients and the discovery of new tumor mechanisms allowed the development of highly precise therapies capable of targeting specific molecular targets.

Personalized oncological therapy fits into this complex context where each patient is treated on the basis of the specific molecular characteristics of his tumor. Molecular target therapies are already a reality: for example, they are used for the treatment of some types of breast cancer, gastrointestinal stromal tumors or chronic myeloid leukemia. These are promising therapies tailored to the genetic characteristics of the patient. Scientific research is working tirelessly to understand how to apply this approach to a larger number of tumors, study the mechanisms of resistance and develop less invasive and more detailed diagnostic tests.

The IBSA Foundation Special Forum aims to discuss the latest discoveries and the objectives of personalized oncological medicine with international experts.

Program

• 2.30 PM  Institutional greetings and introduction
• 2.40 PM Organoids model human disease
  Hans Clevers, Basel (Switzerland)
  
• 3.20 PM Unconventional approaches to cancer therapy 
  René Bernards, Amsterdam (Netherlands)
• 4.00 PM Patient-specific models of multicellular oncogenic competence in metastasis
  Arianna Baggiolini, Bellinzona (Switzerland)
• 4.15 PM Q&A
• 4.45 PM Farewell coffee, Parco Ciani

Moderator
Andrea Alimonti, ETH Zurich (Switzerland), USI Università della Svizzera italiana,
Università degli Studi di Padova (Italy)

Abstract

• Organoids model human disease
  Hans Clevers, Basel (Switzerland)
  
  Organoids are 3D structures that are established from either pluripotent (iPSC/ES) or adult stem cells and capture key characteristics of the represented organ, in terms of architecture, cell type composition, physiology and pathology.  In this seminar, I will discuss the development of adult-stem cell based organoids and will discuss a number of human disease models-in-a-dish that are based on gut, lung, breast and liver organoids.
  
  
• Unconventional approaches to cancer therapy 
  René Bernards, Amsterdam (Netherlands)
  
  Single-agent cancer therapeutics can initially be highly effective, but resistance remains a major challenge. Combining drugs can help avoid resistance, but the number of possible drug combinations vastly exceeds what can be tested clinically, both financially and in terms of patient availability. Rational drug combinations based on a deep understanding of the underlying molecular mechanisms associated with therapy resistance are potentially powerful in the treatment of cancer. In my lecture I will discuss several innovative ways to combine drugs to produce longer-lasting responses in patients. Examples will include synthetic lethal drug combinations, sequential treatment regimen and our very recent approaches to hyperactivate oncogenic signalling in cancer cells as a therapeutic strategy.
  
  
• Patient-specific models of multicellular oncogenic competence in metastasis
  Arianna Baggiolini, Bellinzona (Switzerland)
  
  Oncogenic competence is related to cell fate and cell state, but those are not only cell-intrinsic processes, as they are greatly regulated by the cell extrinsic factors, as the other cells in the microenvironment, and by systemic hormonal and metabolic influences.
  Among the possible metastatic sites, the brain is characterized by distinct metabolic conditions and immune environment. Moreover, the brain is composed of unique cell types as neurons and cells of the glia, like astrocytes and microglia. The study of the human brain microenvironment has always been challenging because of the problematic access to human brain samples, arduous cellular isolation, and culture. The human pluripotent stem cells (hPSCs)-based technologies allow us to build patient-specific 3D brain organoids and address how cancer cells adapt to and remodel the human brain niche.
  
  

Moderator and Speakers

Andrea Alimonti
ETH Zurich (Switzerland), USI Università della Svizzera italiana, Università degli Studi di Padova (Italy)

Head of the Molecular Oncology Laboratory of the Institute of Oncology Research and of the Molecular Oncology Laboratory of the Veneto Institute of Molecular Medicine, Full Professor of Oncology at Università della Svizzera italiana, Full Professor of Pharmacology at Università degli Studi di Padova, Full Professor of Experimental Oncology and Translational Cancer Medicine at ETH Zurich.

Arianna Baggiolini, Bellinzona (Switzerland)
Patient-specific models of multicellular oncogenic competence in metastasis

Dr. Arianna Baggiolini is a Group Leader at the Institute of Oncology Research of BIOS+ in Switzerland. Arianna studies melanoma, the most aggressive skin cancer. She is interested in defining how developmental programs are reactivated during the acquisition of a malignant state and how they regulate tumor formation and progression. Her lab, called Baggiolinilab, combines in vivo models and human pluripotent stem cell (hPSC)-based technologies to address how malignancy is regulated cell-intrinsically and depending on the microenvironment. Arianna has received a number of awards including the Tri-Institutional Breakout Price, the SNSF Starting grant and was elected Leading Edge Fellow 2021.

René Bernards, Amsterdam (Netherlands)
Unconventional approaches to cancer therapy 

René Bernards is a professor of molecular carcinogenesis at the Netherlands Cancer Institute. His laboratory uses functional genomic approaches to find vulnerabilities of cancers that can be exploited therapeutically. His laboratory identified the FDA approved combination of a BRAF inhibitor and an EGFR inhibitor as effective for the treatment of BRAF mutant colon cancer. He also developed the first clinically used gene expression test for early breast cancer prognosis; MammaPrint. 
He is a member of the Royal Netherlands Academy of Sciences, the National Academy of Sciences, the American Academy of Arts and Sciences and a fellow of the AACR Academy.

Hans Clevers, Basel (Switzerland)
Organoids model human disease

Hans Clevers is a Dutch molecular geneticist, cell biologist and stem cell researcher. Hans is currently the Head of pharma Research and Early Development (pRED), and a member of the Corporate Executive Committee of F. Hoffmann-La Roche based in Basel, Switzerland. Previously, Hans headed a research group at the Hubrecht Institute for Developmental Biology and Stem Cell Research and at the Princess Máxima Center for Pediatric Oncology and Oncode where he has remained as an advisor and guest scientist or visiting researcher. He is also a Professor in Molecular Genetics at the University of Utrecht. Hans was group leader at the Hubrecht Institute from 2002 until March 2022.

Han’s research group has spun out a non-profit clinical research organization (CRO), HUB Organoids, where Hans was scientific advisor from 2013-2020. Hans also served at a number of scientific organizations, including on the Board of Directors of the American Association for Cancer Research, and the Scientific Advisory Board of the Swiss Institute for Experimental Cancer Research at the École Polytechnique Fédérale de Lausanne, the Research Institute of Molecular Pathology in Vienna and the Francis Crick Institute in London.

He is currently on many Prize Juries (e.g. Francqui Prize, Brussels; Breakthrough Prize, San Francisco) and also the advisory board of various scientific journals, including The EMBO Journal, Disease Models & Mechanisms, Cell, Stem Cell Reports, Cell Stem Cell, and EMBO Molecular Medicine. From 2014 to 2022, he was also on the editorial committee of the Annual Review of Cancer Biology. Hans has published over 740, highly cited, peer-reviewed papers. Outside of academia, Hans was also a scientific advisor to numerous