Here's a breakdown of some of the highlights from the fifth day of the 2021 European Society for Medical Oncology Congress.
Catch up on some of the latest updates to come from the fifth day of the 2021 ESMO Congress.
A Look at New Generation Therapies in Cancer Treatment
Cancer therapies have rapidly evolved over the years. And the “New generation therapies” session, led by Dr. Carl H. June, MD Director of the Center for Cellular Immunotherapies at the University of Pennsylvania Perelman School of Medicine, explored current and emerging therapies
Dr. June began by explaining the role of CAR T and TCR cells, which have evolved over the past two decades to incorporate our expanding knowledge of tumors. When we look at where we are now in the setting of cancer therapies, we’re looking at CAR T cells as our primary source since they have evolved from the setting of bone marrow transplants.
But moving forward, Dr. June explained that we’re seeing an increase in the use of synthetic biology gene transfer technology for human genome editing. Human genome editing, whether it be in vitro or in vivo, has been a constantly changing field, and an increasing number of tools have been developed for this purpose, including zinc finger nucleases, TALENs, meganucleases, and CRISPR-Cas9.
Dr. June then explained some of the potential uses of human genome editing, including:
- Introducing disease resistance: HIV CCR5 deletion
- Enhancing T cell function: PDC1 (PD-1) deletion, creating “checkpoint resistant” T cells
- Preventing GVHD: TCR deletion, creating “Universal CAR T cells”
He concluded by saying that there are a number of new generation therapies for different types of cancerous disease. He mentioned a range of therapies, ones he’d already spoken about and ones that are newer to the field of oncology:
- CAR T cell-based therapies
- Ionizing radiation
- Chemotherapy
- Targeted small molecule drugs
- Manipulation of the microbiome and cytokines
- Vaccines, oncolytic viruses, and hematopoietic stem cell transplantation
- Antibodies, checkpoint inhibitors, and antibody-drug conjugates
Dr. June ended his presentation by saying that now is an exciting time in oncology, and that targeted checkpoint immunotherapy and standard therapies are moving beyond chemotherapy, radiation, surgery, and checkpoint inhibitor therapy to make treatment less challenging.
Merits & Limitations: Informing Clinical Decision Making with Patient-Derived Cancer Models
Clinical decision-making is an area full of controversy in the field of oncology. And in the “Patient-derived cancer models to inform clinical decision making: More merits or more limitations?” session, led by Samra Turajlic from London, oncology experts shared their perspectives on the merits and limitations of patient-derived cancer models.
To begin, Dr. Turajlic asked the audience the following questions:
- Do you know any example of preclinical research with patient-derived models that had led to therapeutic opportunities effectively applied to patients?
- Is the prospect of developing patient-derived models that incorporate the full complexity of human tumors realistic?
- The reliability of patient-derived xenografts in predicting therapeutic response in patients is superior to that of patient-derived organoids?
The audience provided mixed responses for all three of the questions.
To begin the discussion, Dr. Nicola Valeri, a professor at the Institute of Cancer Research, discussed the merits of patient-derived cancer models.
He explored the evolving landscape of biopsies in precision oncology and focused on the role of functional biopsies as a way to inform clinical decision-making. According to Dr. Valeri, patient-derived cancer models can be split into two types of functional biopsies: patient-derived organoids and patient-derived xenografts. In precision oncology, patient-derived models can inform drug development and help clinicians understand and overcome drug resistance.
Dr. Valeri also noted that while there are many merits, there are some challenges to be aware of. One of the main obstacles is the lack of a microenvironment in a number of these patient-derived models, specifically in patient-derived organoids.
To conclude, Dr. Valeri had a few key take-home messages on the merits of patient-derived models:
- Patient-based models are complementary to molecular pathology in identifying therapeutic strategies
- Co-clinical trials have the potential to inform clinical decisions, and we may be able to move from proof-of-principle studies to clinical routine
- The main challenges we need to address are heterogeneity and the lack of a microenvironment
Following Dr. Valeri, Dr. Livio Trusolino, a professor in the Department of Oncology and the University of Turin School of Medicine, reviewed the limitations of patient-derived cancer models.
Dr. Trusolino began by taking a look at recent clinical trial data on HER2-positive breast and colorectal cancer and argued that in the decision-making process, the impact of innate or adaptive immunity hadn’t been considered.
Dr. Trusolino stressed that patient-derived cancer organoids are a growing platform, still in its adolescence, and that there are a few obstacles preventing this model from effectively informing decision-making, including:
- Population-level studies need to be expanded to include more patients and models
- Readouts of drug sensitivity are heterogenous
- System comparative in vitro and in vivo studies are missing
Organoids can be unpredictable because they cannot take into consideration idiosyncratic differences in patients.
Dr. Turajlic then asked the audience the same questions as before, and their results demonstrated an increase in optimism toward patient-derived cancer models to inform clinical decision making, showing that more education and discussion are needed to better understand the impact these models have on the oncology community.