Gastrointestinal cancer articles within Nature Reviews Clinical Oncology

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  • News & Views |

    The FDA has approved nanoliposomal irinotecan, 5-fluorouracil, leucovorin and oxaliplatin (NALIRIFOX) for patients with metastatic pancreatic adenocarcinoma on the basis of results from the NAPOLI 3 trial, in which this four-drug regimen improved overall survival relative to a doublet regimen. Here we discuss how, in the context of prior results from the PRODIGE 4 trial testing 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (modified FOLFIRINOX), NALIRIFOX does not seem to raise the bar, but rather exposes patients and health-care systems to financial toxicities.

    • Christopher Nevala-Plagemann
    •  & Ignacio Garrido-Laguna

  • News & Views |

    A recent study reported the development and validation of the Liver Artificial Intelligence Diagnosis System (LiAIDS), a fully automated system that integrates deep learning for the diagnosis of liver lesions on the basis of contrast-enhanced CT scans and clinical information. This tool improved diagnostic precision, surpassed the accuracy of junior radiologists (and equalled that of senior radiologists) and streamlined patient triage. These advances underscore the potential of artificial intelligence to enhance hepatology care, although challenges to widespread clinical implementation remain.

    • Jeong Min Lee
    •  & Jae Seok Bae

  • Review Article |

    The development and successful phase III testing of the anti-claudin 18.2 antibody zolbetuximab has provided a novel targeted therapy for the 30–40% of patients with strongly claudin 18.2-positive gastric cancers. Furthermore, the development of an effective targeted therapy for a target that does not have a driver role in cancer development provides a novel drug development paradigm. In this Review, the authors describe the development of claudin 18.2-targeted therapies, including zolbetuximab, as well as novel therapies, including chimeric antigen receptor (CAR) T cells, antibody–drug conjugates and bispecific antibodies, all of which have the potential to expand the number of patients who can derive benefit from claudin 18.2-targeted therapies in the near future.

    • Izuma Nakayama
    • , Changsong Qi
    •  & Kohei Shitara

  • Review Article |

    Patients with early stage hepatocellular carcinoma typically undergo resection, liver transplantation or local ablation; however, 30–50% will have disease recurrence at 3 years. The authors of this Review describe the tumour immune microenvironment and mechanism of action of immunotherapies, and discuss the available evidence from phase II/III trials of neoadjuvant and adjuvant treatment approaches in this setting.

    • Josep M. Llovet
    • , Roser Pinyol
    •  & Richard S. Finn

  • Review Article |

    Hepatocellular carcinoma (HCC) is among the most common causes of cancer-related death globally, and despite improvements in prevention and treatment strategies, continued increases in HCC incidence and mortality are predicted. Cirrhosis remains the major risk factor for HCC, although the underlying aetiology is shifting from virus-related to non-viral liver diseases. In this Review, the authors discuss the changing trends in HCC epidemiology and their implications for screening, prevention and therapy, including opportunities to further improve the management of patients with, or at high risk of, HCC.

    • Amit G. Singal
    • , Fasiha Kanwal
    •  & Josep M. Llovet

  • Review Article |

    The availability of regimens containing one or more immune-checkpoint inhibitors (ICIs) has improved the outcomes in patients with advanced-stage hepatocellular carcinoma. However, clinical benefit from these regimens is difficult to predict, indicating the need for novel biomarkers. In this Review, the authors describe the available evidence on biomarkers to guide the use of ICIs in these patients and discuss promising future research directions.

    • Tim F. Greten
    • , Augusto Villanueva
    •  & Xin W. Wang

  • Review Article |

    Long-term survival rates of patients with gastric cancer remain low, particularly in Western countries. This lack of progress, among other aspects, is likely to reflect a focus on empirical approaches that fail to account for the heterogeneity of gastric cancers. In this Review, the authors summarize the available evidence on the management of patients with early stage gastric cancers, with an emphasis on understanding the underlying biology in order to improve the outcomes in patients with these historically difficult-to-treat tumours.

    • Yuki Hirata
    • , Ayesha Noorani
    •  & Jaffer A. Ajani

  • Review Article |

    Cholangiocarcinoma is a malignancy that continues to be associated with a dismal prognosis, and a better understanding of the disease biology is required to improve early detection and treatment strategies. In this Review, the authors describe key scientific and clinical advances made in this area over the past 5 years, encompassing novel insights into the tumour stroma and immune microenvironment, promising progress in developing liquid biopsy approaches for diagnosis and monitoring, clinical translation of molecularly targeted therapies, emerging immunotherapies and reassessment of the potential role of liver transplantation.

    • Sumera I. Ilyas
    • , Silvia Affo
    •  & Gregory J. Gores

  • Review Article |

    Emerging data indicate a central role for the microbiota in all aspects of colorectal cancer (CRC). Despite this general consensus, understanding the role of specific components of the microbiota in such a way that enables the development of clinical interventions or tools to inform clinical decision-making has thus far proved challenging. In this Review, the authors summarize the role of the microbiota in CRC, including in prevention, in interactions with treatment and as a source of novel biomarkers.

    • Chi Chun Wong
    •  & Jun Yu

  • Review Article |

    Oesophageal cancer is one of the most common malignancies worldwide and is associated with considerable morbidity and mortality. In this Review, the authors highlight advances made across the disease continuum that have improved the management and outcomes of patients with oesophageal cancer. These advances include an increased understanding of the disease biology, improvements in screening, the development of minimally invasive endoscopic monitoring and management technologies, refinement of surgical techniques and perioperative management, and novel radiotherapy and systemic therapy approaches. Continual multidisciplinary efforts across all these aspects of care will further improve patient outcomes.

    • Manish A. Shah
    • , Nasser Altorki
    •  & Julian A. Abrams

  • Review Article |

    Advances in surgical technique and chemotherapy regimens have improved the survival outcomes of patients with pancreatic cancer, although these remain dismal relative to most other solid tumours. Attempts to further improve outcomes have led to increasing research interest in neoadjuvant therapy, which is beginning to improve the outcomes of certain subgroups of patients. In this Review, the authors provide an overview of the various neoadjuvant therapy approaches for patients with pancreatic cancer, including discussions of several promising future research directions

    • Christoph Springfeld
    • , Cristina R. Ferrone
    •  & John Neoptolemos

  • News & Views |

    Allele-specific inhibitors of KRASG12C are approved in non-small-cell lung cancer. Herein, we discuss recent results from the phase I/II KRYSTAL-1 trial of adagrasib alone and in combination with cetuximab in patients with KRASG12C-mutant metastatic colorectal cancer. The combination had promising efficacy and, if confirmed in later-phase trials, concomitant inhibition of EGFR and KRASG12C will present a new paradigm in precision oncology.

    • Federica Di Nicolantonio
    •  & Alberto Bardelli

  • News & Views |

    Neoadjuvant chemotherapy offers a pragmatic alternative to the difficulties associated with delivering timely adjuvant chemotherapy in rectal cancer. Enthusiasm for administering neoadjuvant therapy to all patients with locally advanced rectal cancer is based on data from several phase III trials. Data from the RAPIDO trial are a critical component of this evidence.

    • Robert Glynne-Jones
    •  & James Hollingshead

  • Review Article |

    Neuroendocrine neoplasms (NENs), which can develop in almost any organ and range from indolent neuroendocrine tumours (NETs) to rapidly progressive and fatal neuroendocrine carcinomas (NECs), have historically been approached in a siloed manner according to their specific tissue of origin. However, NETs and NECs across different sites of origin often share genomic and phenotypic characteristics. In this Review, the authors discuss both the clinical and biological commonalities as well as key organ-specific differences of NENs, with a focus on those of the gastrointestinal system and lung. Moreover, they advocate for a cross-cutting, tissue-agnostic approach to drug development for these rare tumours that might enable advances in one disease entity to accelerate research in others, ultimately improving patient care.

    • Kenta Kawasaki
    • , Natasha Rekhtman
    •  & Charles M. Rudin

  • Review Article |

    Peritoneal surface malignancies (PSMs) typically have a poor prognosis, although considerable advances in the understanding and management of these malignancies have been made over the past decade. This Review comprehensively describes the improvements in knowledge of the biology, assessment and classification, perioperative and surgical management, systemic treatment and pre-emptive management of PSMs. The authors also outline future directions for research in this field.

    • Vahan Kepenekian
    • , Aditi Bhatt
    •  & Olivier Glehen

  • Review Article |

    Gastrointestinal stromal tumour (GIST) is the most common form of sarcoma and has become a paradigm of precision medicine owing to the fact that almost all patients harbour one of several known molecule drivers, most of which can be targeted therapeutically. Nevertheless, novel therapeutic strategies are required to overcome the intrinsic resistance of certain subtypes of GIST to existing treatments as well as the acquired resistance that eventually arises in initially sensitive subtypes. This Review describes the biology of GIST, the evolution of the current treatments for this cancer, and the emerging therapeutic agents and approaches that might overcome the remaining clinical challenges.

    • Lillian R. Klug
    • , Homma M. Khosroyani
    •  & Michael C. Heinrich

  • News & Views |

    Patients with pancreatic ductal adenocarcinoma (PDAC) usually have a dismal prognosis, and even after curative resection most patients will have disease relapse and ultimately die. Nonetheless, adjuvant chemotherapy has considerably improved the outcomes of patients who are able to undergo surgery. The PREOPANC trial provides some evidence supporting the use of neoadjuvant therapy for patients with borderline resectable PDACs but not, as claimed, for those with resectable tumours.

    • Christoph Springfeld
    •  & John P. Neoptolemos

  • Review Article |

    Immunotherapy is revolutionizing the treatment of many cancers and hepatocellular carcinoma (HCC) is no exception. This Review describes the heterogeneous immune microenvironments of HCC as well as their links with the various aetiologies underlying this malignancy and with response or resistance to immunotherapies. In addition, the authors provide an overview of the current landscape of clinical trials evaluating immunotherapies across all stages of HCC.

    • Josep M. Llovet
    • , Florian Castet
    •  & Richard S. Finn

  • Comment |

    The treatments oncologists deliver are generally based on evidence from large randomized controlled trials, consistent with practice guidelines, and congruent with the treatments selected by our peers. In this Comment, we use two scenarios to highlight the discomfort clinicians might feel when they are outliers from the guideline-recommended standard of care.

    • Christopher M. Booth
    •  & Aaron M. Goodman

  • Consensus Statement |

    Patients with early-stage rectal cancer might potentially benefit from treatment with an organ-sparing approach, which preserves quality of life owing to avoidance of the need for permanent colostomy. Trials conducted to investigate this have so far been hampered by considerable inter-trial heterogeneity in several key features. In this Consensus Statement, the authors provide guidance on the optimal end points, response assessment time points, follow-up procedures and quality of life measures in an attempt to improve the comparability of clinical research in this area.

    • Emmanouil Fokas
    • , Ane Appelt
    •  & Claus Rödel

  • Review Article |

    Progress in precision medicine for colorectal cancer continues to lag behind the rapid improvements seen in patients with certain other solid tumour types. Nonetheless, owing largely to the availability of better translational models, novel and effective targeted therapy strategies based on tumour biology are beginning to be developed for subsets of patients. In this Review, the authors summarize these developments and discuss future directions in this rapidly evolving area of research.

    • Federica Di Nicolantonio
    • , Pietro Paolo Vitiello
    •  & Alberto Bardelli

  • Review Article |

    Despite considerable progress in the development of targeted therapies, only three biomarkers are currently used to guide the treatment of patients with gastric or gastro-oesophageal junction cancers using approved targeted therapies. Nonetheless, owing to advances in our understanding of tumour biology and sequencing technologies, several novel therapies are expected to soon become available. In this Review, the authors describe current and future biomarker-guided therapies for patients with G/GEJ cancers.

    • Yoshiaki Nakamura
    • , Akihito Kawazoe
    •  & Kohei Shitara

  • Perspective |

    The incidence of early-onset colorectal cancer (CRC) is increasing worldwide for reasons that are currently unclear. Herein, the authors review the current epidemiological, clinical, pathological and molecular understanding of early-onset CRC that occurs in patients ≥50 years of age, drawing contrasts with later-onset CRC. They also discuss future research strategies for improved understanding, prevention, early detection and clinical management of early-onset CRC.

    • Naohiko Akimoto
    • , Tomotaka Ugai
    •  & Shuji Ogino

  • Consensus Statement
    | Open Access

    The analysis of ctDNA obtained from low-volume blood samples has the potential to transform the management of patients with colorectal cancer. Nevertheless, research priorities and minimum standards for sample collection and analysis in this area are currently missing. In this Position Paper, the NCI Colon and Rectal–Anal Task Forces provide a set of recommendations designed to address these challenges and accelerate the implementation of ctDNA in the management of patients with colorectal cancer.

    • Arvind Dasari
    • , Van K. Morris
    •  & Scott Kopetz

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