2026-07-10 | Progressive intestinal tumor cell plasticity, Myc activation, and loss of Lgr5+ tumor stem cell lineage commitment upon Wnt depletion.

Plasticity, the capability of tumor cells to go through phenotypic transitions, promotes colorectal cancer (CRC) progression and treatment resistance. Although plasticity is evident in advanced CRCs, little is known about plasticity in early-stage tumors and tumor stem cells. Here, we demonstrate that a plastic cell state (PCS) is present already in polyps from patients with familial adenomatous polyposis and in mouse intestinal adenomas, in which PCS is associated with PROX1+ tumor stem cells. We furthermore analyzed progressive plasticity upon loss of the canonical wingless-related integration site (Wnt) effector Tcf7 or Lef1 in Apc mutant mice. Deletion of either gene led to emergence of new plastic tumor cell populations, failure of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) tumor stem cell differentiation into enterocyte-like cells, enhanced Myc pathway activation, and increased tumor cell proliferation and tumorigenesis. Together, we demonstrate that PCS is associated with early CRC development and identify multiple potentially druggable mechanisms activated during progressive tumor cell plasticity.

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2026-06-30 | Pelvic desmoid fibromatosis: a diagnostic and therapeutic challenge.

Pelvic desmoid fibromatosis is a rare locally aggressive benign neoplasm, typically presenting in the reproductive age group with lower abdominal pain. Extra-abdominal occurrence being predominant, the pelvic origin of the tumour makes the clinical management a multidisciplinary challenge. Previous surgeries, current or previous pregnancies, and familial adenomatous polyposis have been documented as associated risk factors. Our patient was a young woman with three previous caesarean sections, admitted with a large infiltrative lesion extending into the left pelvic sidewall up to the pelvic bone, causing ipsilateral severe hydroureteronephrosis. Malignancy was suspected due to the infiltrating nature of the lesion on imaging. Due to its proximity to the pelvic veins, preoperative embolisation of the feeding vessel was done. An exploratory laparotomy was performed by a multidisciplinary team. For this deep-seated disease, mass excision was performed along with total hysterectomy, left salpingo-oophorectomy and left ureteroneocystostomy. A part of the lesion infiltrating the presacral fascia was not removed during the primary surgery. Within 24 hours of surgery, she developed critical limb ischaemia in the left limb due to thrombosis in the ipsilateral external iliac artery. An emergency thrombo-embolectomy was performed by the vascular surgeons and thromboprophylaxis continued. Final histopathology confirmed desmoid fibromatosis. For the residual disease, the patient has been under close follow-up and is receiving targeted therapy with oral sorafenib to prevent local progression. Her follow-up imaging showed a decrease in the size of the residual disease and she is asymptomatic currently.

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2026-06-29 | Milestones in Hereditary Colorectal Cancer Research.

This reviews the historical evolution of our understanding of the familial gastrointestinal cancer syndromes. It begins centuries ago with the appreciation of the gastrointestinal polyposis syndromes and the relationship between adenomatous polyps and cancer. However, it was not until 1991 that the APC gene was cloned and linked to familial adenomatous polyposis. Mutated oncogenes and inactivated tumor suppressor genes were discovered in the 1970s, and it was appreciated by the late 1980s that these genetic alterations occurred sequentially during the evolution of gastrointestinal tumors. During the exploration of this process, it was unexpectedly recognized in the early 1990s that hereditary non-polyposis colorectal cancers had a specific mutational signature that was the result of inactivation of the DNA mismatch repair system. This disease involved a unique group of mutational targets, distinctive pathways to tumor development, and the remarkable recognition in the 21st century of novel and highly effective therapeutic approaches to tumor control. Mixed in with these discoveries was the appreciation of multiple unique hamartomatous polyposis syndromes. The progress made over the past 50 years is remarkable and highlights the rapid evolution of new technologies and insightful research.

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