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Immunofluorescence image of a patient-derived colon cancer organoid grown in a 3D in vitro matrix, recapitulating the tumour microanatomy. A strong apical-basal luminal polarity and multiple mitoses are clearly visible in this image. Image supplied by Dr Joseph Regan, Charité— Universitätsmedizin Berlin, Germany
Patients with solid tumours can have unusual patterns of response to anticancer immunotherapy, necessitating the adaptation of traditional response criteria. A recent retrospective analysis of data from patients with four different types of solid tumours treated with the anti-programmed cell death 1 ligand 1 (PD-L1) antibody atezolizumab confirms the previous experience in patients with melanoma and provides several new insights.
Patients value anticancer therapies that provide durable clinical responses; immune-checkpoint inhibitors can provide such benefit for patients with some advanced-stage malignancies, albeit only for a minority of those treated. Modern oncology value frameworks have set efficacy thresholds in an attempt to assess the clinical benefit of anticancer therapeutics. But, is the benefit of durable cancer control reflected in these thresholds?
Despite the rising incidence of cancer in low-income and lower-middle-income countries, very few oncologists are present in these regions — or, in some areas, even none. However, limited evidence of the global oncology workload inequity is available in the literature. Herein, we summarize recent findings that shed some light on this problem and discuss potential oncology workforce solutions.
The PI3K–AKT–mTOR pathway has key roles in tumorigenesis and is dysregulated in most cancers. Consequently, numerous drugs that target key nodes of this pathway have been developed, although few of these agents have been approved for the treatment of cancer. Herein, the authors review the current experience with anticancer therapies that target the PI3K–AKT–mTOR pathway, discuss the challenges that have limited the clinical translation of these agents, and provide perspectives for the future development of these drugs.
The development of cancer involves several epigenomic alterations, and the presence of certain alterations before the development of cancer is associated with cancer risk. In this Review, the authors describe the potential of epigenomics-based assays to predict an individual's risk of cancer, including discussions of technical, practical and societal issues regarding the implementation of such assays.
The combination of immunotherapies with other therapeutic modalities, including anti-angiogenic agents, is currently under investigation to improve the outcomes of patients receiving immunotherapies. In this article, the authors review the effects mediated by anti-angiogenic agents that might increase the efficacy of immunotherapies and discuss the possibility that immunotherapies might increase the efficacy of anti-angiogenic agents and/or promote changes in the tumour vasculature.
The aberrant tumour vasculature and the associated angiogenic factors have been implicated in tumour immune evasion and progression. Herein, the authors provide their perspectives on how normalization of the tumour microenvironment using antiangiogenic agents could potentially increase the effectiveness of immunotherapies and improve the outcomes of patients with cancer. The authors also highlight important considerations for future research in this area.