News & Comment

  • Editorial |

    This month marks one year since the launch of Nature Cancer. As we celebrate our first anniversary, we reflect on the past year and thank the cancer research community for embracing our journal.

  • Clinical Outlook |

    Inhibition of the anti-apoptotic protein BCL-2 has emerged as a highly effective treatment for acute myeloid leukemia; approved lower-intensity venetoclax combination therapies are now being rapidly incorporated into an improved standard of care for this cancer. Here we recount an abbreviated history of venetoclax for acute myeloid leukemia, focusing on a selection of key studies along the path from development into the clinic.

    • Courtney D. DiNardo
    •  & Marina Y. Konopleva
  • News & Views |

    The diversity of tumor cell responses to cyclin-dependent kinase 4/6 (CDK4/6) inhibition in breast cancer is a question not yet fully addressed. A recent study defines the effects of CDK4/6 inhibition on chromatin organization and shows that remodeling of the cancer cell epigenome mediates some of the key biological effects of these targeted therapy agents.

    • Antoni Hurtado
  • News & Views |

    Chronic pancreatitis is a risk factor for pancreatic cancer; however, the mechanisms underlying cellular susceptibility to oncogenic transformation are complex. A recent study reports a damage-associated progenitor cell state, controlled by the transcription factors KLF5 and members of the AP-1 family, that initiates tumorigenesis in mouse models of pancreatic cancer in which the proto-oncogene KRAS is altered.

    • Lindsay M. LaFave
    •  & Jason D. Buenrostro
  • Clinical Outlook |

    Recent preclinical and clinical research has led to exciting advances related to high-grade serous ovarian cancer, from examining its cellular origins to gaining insight into DNA-damage-repair mechanisms that may be leveraged for therapies. Furthermore, studies have demonstrated clinical benefit for inhibition of the polymerase PARP and modulation of the cell cycle, and have identified molecular features related to therapeutic response.

    • Michelle McMullen
    • , Katherine Karakasis
    • , Robert Rottapel
    •  & Amit M. Oza
  • Comment |

    Precision oncology trials based on cancer biomarkers have the potential to improve outcomes by guiding the optimal choice of therapies for patients. For this to be truly achieved, computational methods such as virtual molecular tumor boards, dynamic precision medicine and digital twins are needed to support cohort selection and trial enrollment at scale.

    • Subha Madhavan
    • , Robert A. Beckman
    • , Matthew D. McCoy
    • , Michael J. Pishvaian
    • , Jonathan R. Brody
    •  & Paul Macklin
  • Editorial |

    As COVID-19 continues to surge, it is essential to understand and address the looming crisis of mental-health issues caused or exacerbated by the pandemic.

  • News & Views |

    Achieving depletion of regulatory T cells while sparing tumor-specific effector T cells has long remained an elusive goal of immunotherapy. A new study describing the development of an antibody to the cytokine receptor CD25 optimized to ensure depletion of regulatory T cells without blocking binding of the cytokine IL-2 will reinvigorate interest in this therapeutic avenue.

    • Gavin I. Ellis
    •  & James L. Riley
  • News & Views |

    The response to immunotherapy has been linked to human leukocyte antigen (HLA) genotype in certain cancers. A new study examining the interaction between cancer type–specific mutational exposures and the B44 and B27 HLA supertypes finds that patients with mutant peptides complementary to these supertypes receive the most benefit from immune-checkpoint blockade.

    • Andrea Castro
    •  & Hannah Carter
  • News Feature |

    Beyond the suffering caused by the disease, most patients diagnosed with cancer in the USA face substantial financial hardships associated with their treatments. What underlies the financial toxicity of cancer?

    • Karl Gruber
  • News & Views |

    Immunostimulatory agents such as Toll-like receptor (TLR) agonists have shown promising antitumor efficacy but are associated with therapy-related toxicities when delivered systemically. Immune-stimulating antibody conjugates are now shown to deliver TLR agonists with potent preclinical antitumor activities.

    • Olivier Demaria
    •  & Eric Vivier
  • Editorial |

    Nature Cancer encourages preprint sharing as a valuable means of research dissemination and scholarly communication.

  • News & Views |

    Invariant natural killer T cells (iNKT cells) are innate-like CD1d-restricted T cells that have NK cell–like properties and bear an invariant T cell receptor (iTCR). iNKT cells have shown potential for cancer immunotherapy. A study now shows that stabilization of the iTCR–CD1d complex via a single-chain bi-specific antibody stimulates iNKT cell–mediated anti-tumor immunity.

    • Mark A. Exley
    • , Thomas Gensollen
    •  & Richard S. Blumberg
  • Comment |

    Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here we outline recommendations for future preclinical and translational research in this field.

    • Ihsan Ekin Demir
    • , Carmen Mota Reyes
    • , Wasfi Alrawashdeh
    • , Güralp O. Ceyhan
    • , Sylvie Deborde
    • , Helmut Friess
    • , Kıvanç Görgülü
    • , Rouzanna Istvanffy
    • , David Jungwirth
    • , Rohini Kuner
    • , Maria Maryanovich
    • , Shorook Na’ara
    • , Simon Renders
    • , Jami L. Saloman
    • , Nicole N. Scheff
    • , Hendrik Steenfadt
    • , Pavel Stupakov
    • , Vera Thiel
    • , Divij Verma
    • , Bengi Su Yilmaz
    • , Ruth A. White
    • , Timothy C. Wang
    • , Richard J. Wong
    • , Paul S. Frenette
    • , Ziv Gil
    •  & Brian M. Davis
  • Cancer in Translation |

    Although RET alterations are relatively frequent across tumor types, specific targeting of RET in the clinic has been challenging. Ambrogio, Aggarwal and colleagues provide their views on how mechanistic studies have swiftly translated into powerful targeted therapies in two recent clinical studies that led to the FDA approval of selpercatinib for certain tumors in which RET is altered.

    • Melina E. Marmarelis
    • , Roberto Chiarle
    • , Chiara Ambrogio
    •  & Charu Aggarwal
  • News & Views |

    Tumor-specific changes in DNA methylation are both acquired actively through transcription-coupled processes and passively accumulated over time. Analysis across B cell malignancies now shows that these changes provide insight into the cellular origin as well as the proliferative history of tumors and thereby have diagnostic value and prognostic value, respectively.

    • Paolo Strati
    •  & Michael R. Green
  • News & Views |

    Mitochondrial DNA damage, metabolic disruption and aging have all been associated with cancer. These three threads are now woven together to show that aging-associated somatic mutations to mitochondrial DNA alter mitochondrial serine metabolism to support cell transformation and colon-cancer development.

    • Hiran A. Prag
    •  & Michael P. Murphy
  • News & Views |

    Effective methods for treating retinoblastoma while preserving vision are an unmet clinical need. Subretinal delivery of a hydrogel containing T cells that secrete the cytokine IL-15 and express a chimeric antigen receptor directed at the ganglioside protein GD2 completely controls retinoblastoma in immunocompromised mice, with no obvious damage to the surrounding retina.

    • Anandani Nellan
    •  & Terry J. Fry
  • Editorial |

    Postdoctoral researchers face substantial challenges and stresses that have been exacerbated by the COVID-19 pandemic. Positive action is needed from research institutions, funders and individual investigators to support postdocs and fortify the research endeavor.

  • News & Views |

    Cancer has found a formidable foil in COVID-19, and this has brought to the fore the early concerns that COVID-19 could have a deeper impact on oncology patients. Two studies now provide insights into the enigma surrounding the determinants of the worsening of COVID-19 symptoms in patients with cancer.

    • Vivek Subbiah
  • News & Views |

    Immunotherapy has changed the treatment paradigm for patients with cancer, but patient selection, response assessment and treatment duration require further refinement. A recent study reports that the kinetics of circulating tumor DNA reflect response and resistance to immunotherapy treatment across multiple cancer types and could be used to tailor treatment.

    • Jeanne Tie
  • Editorial |

    The need to address COVID-19 is placing huge demands on biomedical research and regulatory processes. Under pressure, it is essential to uphold high bioethical principles and rigorous standards for the development and approval of medicines.

  • News & Views |

    The urea cycle enzyme argininosuccinate synthase 1 (ASS1) is upregulated in some cancer types. A study now shows that tumor cells with elevated urea cycle activity due to high ASS1 expression enhance gluconeogenesis, enabling a metabolic shift toward serine synthesis and causing purine synthesis addiction for growth and proliferation.

    • Elodie Villa
    •  & Issam Ben-Sahra
  • Editorial |

    Travel restrictions due to COVID-19 have forced the science world to change conference and networking practices. Retaining the positives of virtual interactions should be a priority in the post-pandemic era.

  • News & Views |

    Replication stress fuels chromosomal instability, tumor heterogeneity and therapy resistance. The Sonic hedgehog pathway is now linked to an unorthodox form of replication stress in cerebellar granular-cell progenitors through deregulated firing of DNA replication origins, with implications for the pathogenesis, genomic instability and treatment of medulloblastoma.

    • Apolinar Maya-Mendoza
    •  & Jiri Bartek
  • News & Views |

    Locally injected lipid nanoparticles that deliver RNA to elicit danger signals and simultaneously contain RNA that encodes a membrane-anchored version of the cytokine IL-12 can induce immunogenic cell death in tumors. This multipronged platform induces anticancer immune responses to the injected lesion as well as to distant tumors and hence produces an abscopal effect.

    • Oliver Kepp
    •  & Guido Kroemer
  • News & Views |

    Deep learning can be used to predict genomic alterations on the basis of morphological features learned from digital histopathology. Two independent pan-cancer studies now show that automated learning from digital pathology slides and genomics can potentially delineate broader classes of molecular signatures and prognostic associations across cancer types.

    • Nicolas Coudray
    •  & Aristotelis Tsirigos
  • Editorial |

    Government policies that threaten the international mobility of biomedical students, researchers and physicians stand to imperil scientific progress and innovation at a time when supporting them is paramount.

  • News & Views |

    The pre-metastatic niche is a complex microenvironment formed by the influence of tumor-derived factors on stromal and immune cells at distant sites of disseminated tumor-cell colonization. Signaling through the kinase p38α and regulation of the type I interferon receptor are now linked to formation of the pre-metastatic niche.

    • Sabina Kaczanowska
    •  & Rosandra N. Kaplan
  • News & Views |

    The approval of anti-TNF therapy for colitis over 20 years ago represented a paradigm shift for the treatment of this disease. Anti-TNF therapy is now shown to prevent colitis-associated colon cancer in mice by modifying the gut microbiota composition and transcriptional activity, including genes in Escherichia coli that control colibactin synthesis.

    • Giorgio Trinchieri
  • Editorial |

    Inequalities are prevalent across the spectrum of cancer research and patient care, with destructive repercussions for people and society. We cannot ignore them and must act against the social injustices that perpetuate them.

  • News & Views |

    KEAP1 is a tumor suppressor encoded by a gene commonly mutated in lung cancer. A systematic search for Keap1-mutant cancer vulnerabilities now reveals that Slc33a1 is a context-specific essential gene that represents a promising new anti-cancer target.

    • Luke A. Gilbert
  • News & Views |

    Natural killer (NK) cells serve a critical role in the control of metastasis. NK cells are now shown to preferentially control monoclonal metastases derived from single circulating tumor cells rather than polyclonal metastases derived from cell clusters. These findings provide further evidence that NK cells are linked to metastatic cell immunoediting.

    • Kyohei Nakamura
    •  & Mark J. Smyth
  • Comment |

    The risks posed to patients with cancer by the current COVID-19 pandemic demand rapid structural changes in healthcare delivery, with many positive changes likely to continue long term. An immediate critical reassessment of trial methodology based on clinical and scientific priorities is essential to ensure the resilience of clinical cancer research and optimize patient-centered care.

    • Gary J. Doherty
    • , Mehmet Goksu
    •  & Bruno H. R. de Paula
  • Comment |

    The COVID-19 pandemic has disrupted the spectrum of cancer care, including delaying diagnoses and treatment and halting clinical trials. In response, healthcare systems are rapidly reorganizing cancer services to ensure that patients continue to receive essential care while minimizing exposure to SARS-CoV-2 infection.

    • Mike Richards
    • , Michael Anderson
    • , Paul Carter
    • , Benjamin L. Ebert
    •  & Elias Mossialos
  • News & Views |

    Immune-checkpoint blockade holds great promise in cancer therapy; however, T cell–specific checkpoint inhibitors are not effective for all patients with cancer. The transcription factor c-Rel is now shown to regulate pro-inflammatory polarization of myeloid cells and modulate anti-tumor immune responses.

    • Hideyuki Takahashi
    •  & Judy Varner
  • Editorial |

    The urgent need to address COVID-19 has highlighted the delicate relationships among science, politics and the media. To achieve a successful long-term response to the pandemic, stakeholders need to be guided by data, integrity and a sense of responsibility toward the public.

  • News & Views |

    Studies of the tumor microenvironment have provided fundamental insights into cancer progression. A new study now delineates the dynamics of immune-cell alterations at the single-cell level and across stages of multiple myeloma, elucidating the microenvironmental changes involved in the precursor states of the disease.

    • Qiming Zhang
    •  & Zemin Zhang
  • Comment |

    Crowdsourcing efforts are currently underway to collect and analyze data from patients with cancer who are affected by the COVID-19 pandemic. These community-led initiatives will fill key knowledge gaps to tackle crucial clinical questions on the complexities of infection with the causative coronavirus SARS-Cov-2 in the large, heterogeneous group of vulnerable patients with cancer.

    • Aakash Desai
    • , Jeremy Warner
    • , Nicole Kuderer
    • , Mike Thompson
    • , Corrie Painter
    • , Gary Lyman
    •  & Gilberto Lopes
  • Cancer in Translation |

    Although cancer genomics is a powerful tool to understand cancer and develop diagnostic tools, the contribution of the microbiome in cancer diagnosis and clinical assessment is much less studied. Elinav, Greten and colleagues provide their respective views on how studying cancer metagenomes could facilitate identification, diagnosis and staging of different tumor types.

    • Lorenz Adlung
    • , Eran Elinav
    • , Tim F. Greten
    •  & Firouzeh Korangy
  • News & Views |

    Small-cell lung cancer rapidly develops resistance to standard-of-care therapy. Two papers now establish xenograft models derived from patient-derived circulating tumor cells and show that initially homogeneous, chemoresponsive tumors rapidly recur as heterogeneous drug-refractory disease.

    • Anton Berns
  • News & Views |

    Despite recent advances in cancer treatment, metastasis and therapy resistance remain among the major causes of cancer-related deaths worldwide. A recent pan-cancer study provides a comprehensive molecular profile of advanced and post-therapy tumors, integrating whole-genome and transcriptomic analysis with clinical outcomes.

    • Esther Rheinbay
  • Editorial |

    As the COVID-19 pandemic sweeps through the world, we must reassess the principles that guide our individual and collective responses and the way we operate in society. In the face of crisis, we must lead with science and humanity.

  • News & Views |

    Dysregulation of innate immune signaling in cancer can be pro-tumorigenic and can promote adaptive resistance to targeted therapies. Type I interferon signaling is now shown to promote survival following inhibition of the kinase EGFR, even in cells that are not ‘addicted’ to EGFR signaling.

    • Ryohei Yoshida
    •  & David A. Barbie
  • Editorial |

    The field of cancer genomics has been advancing at a rapid pace, opening up a wealth of possibilities for translational applications. In this issue, we are excited to launch a Series of commissioned articles that explore the role of genomics in cancer research and oncology, from current achievements to future directions.

  • News & Views |

    Although many metabolic dependencies of cancer cells are well documented, altered cancer metabolism has not always been considered an active driver of tumorigenesis. Restrictive glutamine availability is now shown to promote colorectal cancer by lowering α-ketoglutarate levels and thereby promoting DNA hypermethylation, Wnt signaling and cellular de-differentiation.

    • Dana Krauß
    •  & Eyal Gottlieb
  • Cancer in Translation |

    A new suite of studies from the Pan Cancer Analysis of Whole Genomes (PCAWG) Consortium provides the most detailed resolution of cancer genomes to date, extending our knowledge of driver genes, mutational features, structural alterations and more. Kreisberg, Ideker, Mills and Meric-Bernstam discuss the foundational and translational insights gained from this project.

    • Jason F. Kreisberg
    • , Trey Ideker
    • , Funda Meric-Bernstam
    •  & Gordon Mills
  • News & Views |

    To demonstrate the long-range effects of CD8+ T cell–secreted interferon-γ on bystander tumor cells, two studies now use mosaic models of antigen loss in tumors combined with intravital imaging. Factors that influence the length scale of diffusible signals could shape disease progression in cancer and autoimmunity.

    • Kenneth H. Hu
    •  & Matthew F. Krummel