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Nature Reviews Cancer


Melanoma: a global perspective


Most of our current knowledge of melanoma is derived from the study of patients from populations of European descent, for whom public health, sun protection initiatives and screening measures have appreciably decreased disease mortality. Notably, some melanoma subtypes that most commonly develop in other populations

Cancer models: Tailored mouse models


To advance preclinical research, two groups have developed mouse models of metastatic colorectal cancer using the transplantation of engineered organoids.

Tumour immunology: LAP targeting reduces tolerogenic cells in cancer


Anti-LAP antibodies show promising anticancer properties.

Immunotherapy: Macrophages steal the show


Pittet and collaborators show that macrophages can remove anti-PD1 antibodies from T cells, blunting their response, whereas Weissman and colleagues demonstrate that macrophages also express PD1 on their surface, which impairs their phagocytic activity.

Leukaemia: Unravelling the heterogeneity of cancer stem cells


Giustacchini, Thongjuea, et al. have developed a method to sensitively detect somatic mutations and analyze whole transcriptomes of the same single cell. Application of this technique to chronic myeloid leukaemia (CML) patient samples revealed heterogeneous CML stem cell populations with likely roles in CML progression and resistance to therapy.

Tumour metabolism: Losing that remaining fat


Recurrence of breast cancer can result from minimal residual disease. Havas et al. used mouse models and organoid cultures to show that residual cancer cells following tumour regression have a transcriptionally distinct state from that of normal epithelium and primary tumour cells. The transcriptomic

Cancer Models: Modeling clear cell renal cell carcinoma


A new autochthonous genetically engineered mouse model of clear cell renal cell carcinoma (ccRCC) has been developed by combining deletion of the von Hippel–Lindau tumour suppressor gene (Vhl), Trp53 and Rb1 specifically in renal epithelial cells. Tumours arose from proximal tubule

Targeted therapies: Expanding the use of PARP inhibitors


Inhibition of poly(ADP-ribose) polymerase (PARP), which is part of the single-strand break DNA repair pathway, is synthetic lethal with BRCA1- or BRCA2-induced defects in the homologous recombination (HR) DNA repair pathway. Pharmacological PARP inhibitors (PARPis) have been successfully used in cancers with BRCA

Imaging of anticancer drug action in single cells


Imaging is widely used in anticancer drug development, typically for whole-body tracking of labelled drugs to different organs or to assess drug efficacy through volumetric measurements. However, increasing attention has been drawn to pharmacology at the single-cell level. Diverse cell types, including cancer-associated immune cells,

Transposable elements in cancer


Transposable elements give rise to interspersed repeats, sequences that comprise most of our genomes. These mobile DNAs have been historically underappreciated — both because they have been presumed to be unimportant, and because their high copy number and variability pose unique technical challenges. Neither impediment

Turning the tide in myelodysplastic/myeloproliferative neoplasms


Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) are aggressive myeloid malignancies recognized as a distinct category owing to their unique combination of dysplastic and proliferative features. Although current classification schemes still emphasize morphology and exclusionary criteria, disease-defining somatic mutations and/or germline predisposition alleles are increasingly incorporated into diagnostic

Common pitfalls in preclinical cancer target validation


An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being