Cancer therapy articles within Nature

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  • Article
    | Open Access

    The transcription factor FOXO1 has a key role in human T cell memory, and manipulating FOXO1 expression could provide a way to enhance CAR T cell therapies by increasing CAR T cell persistence and antitumour activity.

    • Alexander E. Doan
    • , Katherine P. Mueller
    •  & Evan W. Weber

  • Article
    | Open Access

    RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

    • Matthew Holderfield
    • , Bianca J. Lee
    •  & Mallika Singh

  • Article
    | Open Access

    Poly(ADP-ribose) polymerase 1 (PARP1) functions together with TIMELESS and TIPIN to protect the replisome in early S phase from transcription–replication conflicts, and inhibiting PARP1 enzymatic activity may suffice for treatment efficacy in homologous recombination-deficient settings.

    • Michalis Petropoulos
    • , Angeliki Karamichali
    •  & Thanos D. Halazonetis

  • Article
    | Open Access

    We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

    • Julie George
    • , Lukas Maas
    •  & Roman K. Thomas

  • Article
    | Open Access

    Peptide-centric chimeric antigen receptors (PC-CARs) provide a platform to address the challenges involved in targeting intracellular oncoproteins, and PC-CARs based on the neuroblastoma-dependency gene PHOX2B induce elimination of aggressive tumors.

    • Mark Yarmarkovich
    • , Quinlen F. Marshall
    •  & John M. Maris

  • Article |

    Genomics analyses reveal that in vitro culture of CAR T cells can lead to reactivation of a latent herpesvirus, which might be involved in complications in patients receiving associated cell therapies.

    • Caleb A. Lareau
    • , Yajie Yin
    •  & Ansuman T. Satpathy

  • Article
    | Open Access

    An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

    • Christina K. Baumgartner
    • , Hakimeh Ebrahimi-Nik
    •  & Robert T. Manguso

  • Article |

    A CRISPR–Cas9 screen in a tumour mouse model identifies CD300ld as a tumour receptor on polymorphonuclear myeloid-derived suppressor cells and in vivo experiments indicate that it is a promising target for cancer immunotherapy.

    • Chaoxiong Wang
    • , Xichen Zheng
    •  & Min Luo

  • Article |

    Netrin-1 is upregulated in cancer models that undergo spontaneous epithelial-to-mesenchymal transition, and its targeting blocks the progression of tumour cells to a late mesenchymal state, suggesting possible therapeutic applications.

    • Justine Lengrand
    • , Ievgenia Pastushenko
    •  & Cédric Blanpain

  • Perspective |

    This Perspective reviews advances in the understanding of the intersection between the DNA damage response and the response to immune checkpoint blockade therapy, and discusses how developments in the field could lead to improved anti-cancer therapies.

    • Anand V. R. Kornepati
    • , Cody M. Rogers
    •  & Tyler J. Curiel

  • Article |

    Induction of APOBEC3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that its suppression may represent a potential therapeutic strategy in the prevention of acquired resistance to lung cancer targeted therapy.

    • Hideko Isozaki
    • , Ramin Sakhtemani
    •  & Aaron N. Hata

  • Article
    | Open Access

    A non-covalent inhibitor that binds preferentially to the inactive state of KRAS while sparing NRAS and HRAS is reported, indicating that most KRAS oncoproteins cycle between an active state and an inactive state in cancer cells.

    • Dongsung Kim
    • , Lorenz Herdeis
    •  & Piro Lito

  • Article
    | Open Access

    A phase I clinical trial of an adjuvant personalized mRNA neoantigen vaccine, autogene cevumeran, in patients with pancreatic ductal carcinoma demonstrates that the vaccine can induce T cell activity that may correlate with delayed recurrence of disease.

    • Luis A. Rojas
    • , Zachary Sethna
    •  & Vinod P. Balachandran

  • Article
    | Open Access

    RHOJ regulates epithelial-to-mesenchymal-transition-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy.

    • Maud Debaugnies
    • , Sara Rodríguez-Acebes
    •  & Cédric Blanpain

  • Article |

    Somatic mutations in MEN1 are identified in patients with leukaemia treated with a novel chromatin-targeting therapy, and the mechanism by which these mutations mediate therapeutic resistance is characterized.

    • Florian Perner
    • , Eytan M. Stein
    •  & Sheng F. Cai

  • Article
    | Open Access

    Revumenib, a potent and selective oral inhibitor of the menin–KMT2A interaction, is associated with a low frequency of treatment-related adverse events and promising clinical activity in patients with relapsed or refractory acute leukaemia.

    • Ghayas C. Issa
    • , Ibrahim Aldoss
    •  & Eytan M. Stein

  • Article |

    Logic gating is used to develop a CAR T cell platform that is highly specific and allows the activity of T cells to be restricted to the encounter of two antigens, thus reducing on-target, off-tumour toxicity.

    • Aidan M. Tousley
    • , Maria Caterina Rotiroti
    •  & Robbie G. Majzner

  • Article
    | Open Access

    Indole-3-acetic acid (3-IAA), a tryptophan metabolite derived from the gut microbiota, is associated with a better response to chemotherapy in pancreatic ductal adenocarcinoma (PDAC), and dietary interventions could have a role in the treatment of PDAC.

    • Joseph Tintelnot
    • , Yang Xu
    •  & Nicola Gagliani

  • Article
    | Open Access

    Patients with resectable clinical stage III or oligometastatic stage IV melanoma were given neoadjuvant relatlimab and nivolumab combination immunotherapy, which induced a high pathologic complete response rate, indicating the efficacy and safety of this regimen.

    • Rodabe N. Amaria
    • , Michael Postow
    •  & Hussein A. Tawbi

  • Article
    | Open Access

    Binding of the PD1-IL2v immunocytokine to PD-1 and IL-2Rβγ on the same cell leads to an alternative differentiation of stem-like CD8+ T cells into better effectors rather than exhausted T cells in models of both chronic infection and cancer.

    • Laura Codarri Deak
    • , Valeria Nicolini
    •  & Pablo Umaña

  • Article
    | Open Access

    Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.

    • Takahiro Seki
    • , Yunlong Yang
    •  & Yihai Cao

  • Article |

    Deep whole-genome sequencing of serial blood samples and matched metastatic tissue reveals that circulating tumour DNA profiling enables detailed study of treatment-driven subclone dynamics, epigenomics and genome-wide somatic evolution in metastatic human cancers.

    • Cameron Herberts
    • , Matti Annala
    •  & Alexander W. Wyatt

  • Article |

    A genetic lineage-tracing system in human colorectal organoids identifies a population of dormant cancer cells that persists during chemotherapy and enables cancer regrowth, and the cell-adhesion molecule COL17A1 has a key role in the process of breaking dormancy.

    • Yuki Ohta
    • , Masayuki Fujii
    •  & Toshiro Sato

  • Article
    | Open Access

    Synthetic chimeric orthogonal IL-2 receptors that incorporate the intracellular domain of receptors for other γ-chain cytokines such as IL-9 can reroute orthogonal signalling and alter the phenotype of T cells to improve anti-tumour responses.

    • Anusha Kalbasi
    • , Mikko Siurala
    •  & K. Christopher Garcia

  • Article |

    A small molecule can bypass the RNA-editing enzyme ADAR1 to directly activate the Z-form nucleic acid sensor ZBP1, induce necroptosis in tumour fibroblasts and reverse resistance to immune checkpoint blockade in mouse models of melanoma.

    • Ting Zhang
    • , Chaoran Yin
    •  & Siddharth Balachandran

  • Article |

    A translationally silent KRASG60G mutation, preventing the formation of a cryptic splice donor site and  enabling expression of KRAS(Q61K), reveals a vulnerability in RASQ61 cancers that are therapeutically exploitable in a mutant-selective manner.

    • Yoshihisa Kobayashi
    • , Chhayheng Chhoeu
    •  & Pasi A. Jänne

  • Article
    | Open Access

    A survey of potency and efficacy of 2,025 clinically relevant two-drug combinations against 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines identifies rare synergistic effects of anticancer drugs, informing rational combination treatments for specific cancer subtypes.

    • Patricia Jaaks
    • , Elizabeth A. Coker
    •  & Mathew J. Garnett

  • Article
    | Open Access

    PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.

    • Lanbo Xiao
    • , Abhijit Parolia
    •  & Arul M. Chinnaiyan

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