Latest Research
All publications from the Cancer3.AI database, newest first.
Apoptotic modulators enhance oncolytic virus-induced cytokine killing in acute myeloid leukaemia (AML).
Askar B, et al
Researchers investigated whether combining oncolytic viruses (OVs) with apoptosis-promoting drugs called SMAC/BH3 mimetics could improve treatment outcomes for acute myeloid leukaemia (AML), a blood cancer with a five-year survival rate of only 5–15% in adults. The study used human AML cell lines, healthy donor immune cells, and patient samples to examine how OVs stimulate immune cells to release inflammatory cytokines that kill cancer cells. Scientists found that SMAC/BH3 mimetics significantly boosted this cytokine-mediated killing, with interferon-alpha and TNF-alpha identified as key mediators of AML cell death, and the best drug combination depending on the specific AML subtype. Critically, the apoptotic modulators remained effective even when paired with UV-inactivated virus, suggesting the approach does not require active viral replication. These findings establish a novel reovirus-based combination immunotherapy strategy that could offer a better-tolerated alternative to intensive chemotherapy, particularly for elderly AML patients who are unable to withstand standard treatments.
British journal of cancer
Source →Acute rheumatic fever mimicking thyroid storm in an adolescent: a case report.
Zhang T, et al
This case report describes a rare and diagnostically challenging presentation in which an adolescent patient with acute rheumatic fever displayed clinical features closely resembling thyroid storm, a life-threatening endocrine emergency. Acute rheumatic fever is an inflammatory condition triggered by group A streptococcal infection that can affect the heart, joints, skin, and nervous system, while thyroid storm involves extreme overactivity of the thyroid gland with overlapping symptoms such as fever, rapid heart rate, and neurological changes. The authors document how this overlap in clinical signs led to significant diagnostic uncertainty, highlighting the importance of considering infectious and inflammatory conditions in the differential diagnosis of suspected thyroid emergencies. This case underscores the need for clinicians, particularly pediatricians, to maintain a broad differential diagnosis when evaluating adolescents presenting with symptoms of hypermetabolic states. Accurate and timely diagnosis is critical, as the treatment approaches for these two conditions differ substantially and misdiagnosis could lead to inappropriate or delayed care.
BMC pediatrics
Source →Clinicopathological and molecular characterization of tumor-associated macrophages in sporadic and Xeroderma Pigmentosum-related cutaneous melanoma.
Chikhaoui A, et al
A new study published in BMC Cancer investigated the clinicopathological and molecular features of tumor-associated macrophages (TAMs) in two distinct forms of cutaneous melanoma: the common sporadic type and the rarer form linked to Xeroderma Pigmentosum (XP), a genetic disorder that severely impairs DNA repair and dramatically increases cancer risk. TAMs are immune cells that infiltrate tumors and can either promote or suppress cancer progression, making them important targets for understanding the tumor microenvironment. By comparing TAM characteristics across these two melanoma populations, researchers sought to determine whether the underlying genetic context of the disease influences macrophage behavior and distribution within the tumor. The findings contribute to a deeper understanding of how immune cell composition differs between genetically predisposed and sporadic melanoma cases, which may have implications for immunotherapy strategies. This work is particularly relevant for patients with Xeroderma Pigmentosum, who face a dramatically elevated melanoma risk and for whom tailored therapeutic approaches are urgently needed.
BMC cancer
Source →Overcoming MEN1-mediated resistance with menin inhibitor switching in KMT2A-rearranged acute myeloid leukemia.
Chin K, et al
Researchers investigated a critical challenge in treating KMT2A-rearranged acute myeloid leukemia (AML): the development of resistance to menin inhibitors, a promising class of targeted therapies, through mutations in the MEN1 gene encoding the menin protein itself. The study examined whether switching from one menin inhibitor to another could overcome this resistance mechanism in patients whose disease had stopped responding to initial treatment. The findings demonstrated that menin inhibitor switching can restore sensitivity and achieve clinical responses in patients who developed MEN1-mediated resistance, suggesting that acquired resistance is not an insurmountable barrier. This work is clinically significant because KMT2A-rearranged AML is an aggressive and difficult-to-treat subtype, and menin inhibitors represent one of the few targeted therapeutic options available. The results provide a strategic framework for sequencing menin inhibitor therapies and offer renewed hope for patients who relapse on first-line menin inhibitor treatment.
Leukemia
Source →MESH1 functions as a metazoan PAPS phosphatase to regulate sulfation.
Lin C, et al
This study investigated the molecular machinery controlling biological sulfation, a chemical modification essential for the function of many proteins, sugars, and lipids throughout the body. Researchers discovered that a protein called MESH1 (also known as HDDC3) serves as the long-sought phosphatase enzyme that breaks down PAPS — the universal sulfate donor molecule used in every biological sulfation reaction — into its component parts. Using X-ray crystallography, cell culture knockdown experiments, and animal models including brachymorphic mice and the roundworm C. elegans, the team demonstrated that MESH1 localizes to the Golgi apparatus, where it regulates the availability of PAPS and thereby controls the production of sulfated glycosaminoglycans, structural molecules critical for healthy cartilage and connective tissue. Strikingly, eliminating Mesh1 in mice with pre-existing sulfation deficiency significantly elevated sulfated glycosaminoglycan levels in joint cartilage and improved bone density, demonstrating a direct, therapeutically relevant effect. These findings close a major gap in our understanding of sulfation biology and establish MESH1 as a promising drug target for skeletal dysplasias and other disorders driven by insufficient sulfation.
Nature chemical biology
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