Continuing the Conversation
Authors: Luis A. Diaz, Lewis C. Cantley
Journal: Cancer Discovery (2024)

In last year's editorial (1), we reiterated that the central mission of Cancer Discovery is to bring together basic, translational, and clinical cancer researchers to catalyze a discussion of the most impactful and innovative science and that our goal is to work with the cancer research community to amplify new ways of thinking. We are not interested in considering content simply because it is likely to be highly cited or influence journal metrics in the near term based on current scientific fads or publishing trends. We are most excited by thinking years ahead to unexplored frontiers of cancer research and tackling problems in ways that have not been done before. Bold and creative thinking is needed to make measurable progress in understanding the fundamental nature of cancer and ultimately improve outcomes for patients.In that spirit, we are pleased to present an entirely community-driven issue devoted to reconceptualizing the way we approach cancer in the hopes of expanding viewpoints, galvanizing ideas, and opening new avenues of discourse.In February 2022, President Biden reignited the Cancer Moonshot to end cancer as we know it with a goal of reducing the cancer-related death rate by at least 50% over the next 25 years. As current NIH Director (and former NCI Director) Monica Bertagnolli, Danielle Carnival, and Elizabeth Jaffee noted in the journal last year (2), we will not meet this goal if we simply maintain the status quo. Significant investment and innovation is needed in fundamental, translational, and clinical research as well as in public health and cancer care delivery. As President Biden's first term draws to a close, Catharine Young and Danielle Carnival provide an overview of the progress of the Cancer Moonshot thus far toward its goal of ending cancer as we know it, not only in the US, but worldwide (page 552).During her tenure as NCI Director in 2023, Monica Bertagnolli announced the creation of a National Cancer Plan with eight goals aimed at preventing cancer, reducing mortality from cancer, and maximizing quality of life for people with cancer (https://nationalcancerplan.cancer.gov/). In this issue, we are pleased to share NCI Director W. Kimryn Rathmell's inaugural commentary for the cancer research community outlining her vision of the National Cancer Plan and presenting it as a framework for a new era in cancer research and patient care (page 555).In 2023, after a global consultation with the cancer research community, Cancer Grand Challenges—a partnership between Cancer Research UK and the NCI—announced nine ambitious challenges of complexity and scale that can only be solved by interdisciplinary, international collaborations (3). This year, five new teams have been chosen to move their ideas forward and decipher the T-cell receptor cancer recognition code (Team MATCHMAKERS); determine why the incidence of early-onset cancers in adults is rising globally (Team PROSPECT); generate functional and mechanistic insights into how genetics, biology, and social determinants affect cancer risk and outcomes in diverse populations to motivate interventions to reduce cancer inequities (Team SAMBAI); and develop new therapeutics to target oncogenic drivers of pediatric solid tumors (Team KOODAC and Team PROTECT) (page 559). We congratulate the new teams and eagerly anticipate sharing the progress that will be made.Last fall, we issued the journal's first-ever call for commentaries, asking the community to submit proposals for topics that challenge existing paradigms or shed new light on arising issues or emerging topics in the field. We were blown away by the number of proposals submitted, the spectrum of cancer researchers who answered the call, and the diversity of ideas. It was extremely difficult to choose among the proposals. Our aim was to not only cover the entirety of the journal's scope but also to pick those that looked at old problems in a new way, incisively pointed out where changes to the status quo were most needed, and proposed a way forward. The final collection (indicated by the image from the cover) includes discussions on how to advance cancer prevention and interception principles amid ever-increasing insights into premalignancy, calls to reconceptualize cancer and deployment of cancer therapy within a framework of the relationship between tumor and host, viewpoints on reimagin­ing drug development, clinical trials, and population studies in the age of precision medicine and big data with an eye toward reducing health disparities, and deliberations on how rapidly developing technologies should be best harnessed to accelerate progress against cancer. We found it fascinating how different ideas across the commentaries ended up connecting, and we hope you will agree that the entire collection is as enlightening as it is inspiring.The Hallmarks of Cancer continues to be a defining conceptual framework in the field, and we were proud to share Douglas Hanahan's most recent update with new hallmarks and emerging characteristics in 2022 (4). What's next for the Hallmarks? In this issue, we asked early-career investigators where they think research focused on each Hallmark is headed (page 674). Also in this issue, given emerging evidence that precancerous lesions can be biologically distinct from fully developed cancers, members of the NCI's Translational and Basic Science Research in Early Lesions Consortium propose the Hallmarks of Precancer, a set of generalizable principles that govern early lesions (page 683). We hope these perspectives will spur a rigorous discussion and invite the cancer research community to join together to create a shared legacy of the Hallmarks of Cancer.This special issue exemplifies our vision for Cancer Discovery to be the venue for cancer researchers across the world and at all stages of their careers to join together to address key unanswered questions or overcome long-standing obstacles to progress in innovative ways. The concepts raised in these pages set the stage for new areas of inquiry, and we want to hear about your discoveries in coming months and years. We look forward to continuing the conversation.L.A. Diaz is a member of the board of directors of Quest Diagnostics and Epitope. He is a compensated consultant to PetDx, Innovatus CP, Se'er, Delfi, Blackstone, and Neophore. L.A. Diaz is an inventor of multiple licensed patents related to technology for circulating tumor DNA analyses and mismatch repair deficiency for diagnosis and therapy. Some of these licenses and relationships are associated with equity or royalty payments to the inventors. He holds equity in Quest Diagnostics, Epitope, PetDx, Se'er, Delfi, and Neophore. He divested his equity in Personal Genome Diagnostics to LabCorp in February 2022 and divested his equity in Thrive Earlier Detection to Exact Biosciences in January 2021. His spouse holds equity in Amgen. The terms of all these arrangements are being managed by Memorial Sloan Kettering in accordance with their conflict-of-interest policy. No disclosures were reported by the other author.