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Dana-Farber Cancer Institute News - April 15, 2023

Health and Fitness

April 19, 2023

From: Dana-Farber Cancer Institute

This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from March 16 through March 31.

If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing [email protected]


For more about Dana-Farber science, tune in to our Unraveled podcast. The second season is now available at dana-farber.org/unraveled, or wherever you get your podcasts.

Journal of Clinical Oncology

ASCO Ethical Guidance for the US Oncology Community Where Reproductive Health Care Is Limited by Law

Jimenez RB, Rosenberg AR

The decision in Dobbs v Jackson Women's Health Organization overturned federal protections for abortion rights, making way for states to enact abortion bans with or without exceptions for the health or life of the pregnant patient. Patient care across many areas of medicine including oncology continues to be affected. Although the change in the legal landscape is widely felt, the core ethical considerations for physicians do not change because of restrictions on the practice of medicine. ASCO offers this guidance to assist US oncologists and institutions who must balance limitations with established ethical duties. This paper articulates principles for cancer care and pregnancy, offers a framework for ethical reflection and action for oncologists who care for pregnant patients, and makes recommendations for individual and institutional action to support evidence-based, patient-centered care in the United States where abortion is illegal or access is limited.

JAMA Oncology

An Oncology Artificial Intelligence Fact Sheet for Cancer Clinicians

Bitterman DS, Kamal A, Mak RH

Artificial intelligence (AI) systems — which consist of an AI algorithm and the contexts in which it is deployed — are increasingly obtaining U.S. Food and Drug Administration (FDA) approval and entering the oncology clinic. Artificial intelligence can now assist with fundamental steps of cancer care, including cancer screening, clinical risk prediction, and radiotherapy planning. But especially in early days of implementation, there are risks associated with inappropriate AI use, as well as unknown effects of human factors on system performance in the clinic. Efficiently educating clinicians about AI systems is paramount at this inflection point of AI integration into cancer care.

Nature Nanotechnology

Author Correction: Multi-Micron Crisscross Structures Grown from DNA-Origami Slats

Wintersinger CM, Minev D, Ershova A, Sasaki HM, Gowri G, Berengut JF, Corea-Dilbert FE, Yin P, Shih WM

In the version of this article initially published, Supplementary Data 5-8 were missing. The error has been corrected in the HTML and PDF versions of the article.

Science

A Common Cancer at an Uncommon Age

Giannakis M, Ng K

Early-onset colorectal cancer (EOCRC), also called young-onset colorectal cancer, is defined as CRC diagnosed in individuals aged less than 50 years. EOCRC is increasing globally and anticipated to become the leading cause of cancer death in individuals aged 20 to 49 in the US by 2030. Since the 1990s, the age-adjusted incidence of EOCRC has risen at an alarming rate of 2 to 4% per year in many countries, with even sharper increases in individuals younger than 30 years. This is despite a reduction in overall CRC incidence that is likely attributable to improved screening and prevention in older individuals. The exact reasons and pathophysiology behind the rising incidence of EOCRC remain unknown. Currently, only limited studies exist and they have focused on single aspects of EOCRC etiology. A multidisciplinary path forward is needed to expand the understanding of this increasingly prevalent problem.

Science

Structures of BIRC6-Client Complexes Provide a Mechanism of SMAC-Mediated Release of Caspases

Hunkeler M, Jin CY, Fischer ES

Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis proteins (IAPs) are the principal actors that restrain caspase activity and are therefore attractive therapeutic targets. IAPs, in turn, are regulated by mitochondria-derived proapoptotic factors such as SMAC and HTRA2. Through a series of cryo-electron microscopy structures of full-length human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2, we provide a molecular understanding for BIRC6-mediated caspase inhibition and its release by SMAC. The architecture of BIRC6, together with near-irreversible binding of SMAC, elucidates how the IAP inhibitor SMAC can effectively control a processive ubiquitin ligase to respond to apoptotic stimuli.