Despite a recent overall decrease in colorectal cancer (CRC) incidence and mortality, there has been a significant rise in CRC diagnoses in young adults. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed before the age of 50. Possible predisposing conditions include not only genetic syndromes but also other risk factors, such as microbiome alteration, antibiotic exposure, obesity, diabetes mellitus, and inflammatory bowel disease. EOCRC tends to be diagnosed later than in the older counterpart because of a lack of awareness and the fact that screening for CRC usually starts at the age of 50. Furthermore, CRC in young adults seems to be related to unique molecular features and more aggressive clinical behavior. This paper aims to provide an in-depth review of this poorly understood subject, with a comprehensive review of the state of the art and considerations for future perspectives.

Key Clinical Message: Germline pathogenic variants (PV) of thePALB2tumor suppressor gene are associated with an increased risk of breast, pancreatic, and ovarian cancer. In previous research,PALB2‐associated breast cancer showed aggressive clinicopathological phenotypes, particularly triple‐negative subtype, and higher mortality regardless of tumor stage, type of chemotherapy nor hormone receptor status. The identification of this germline alteration may have an impact on clinical management of breast cancer (BC) from the surgical approach to the systemic treatment choice. We herein report the case of a patient with a germline PV ofPALB2, diagnosed with locally advanced PD‐L1 positive triple‐negative BC, who progressed after an immune checkpoint inhibitor (ICI)‐containing regimen and then experienced a pathologic complete response after platinum‐based chemotherapy. This case report hints a major role of the germlinePALB2alteration compared to the PD‐L1 expression as cancer driver and gives us the opportunity to extensively review and discuss the available literature on the optimal management ofPALB2‐associated BC. Overall, our case report and review of the literature provide additional evidence that the germline analysis ofPALB2gene should be included in routine genetic testing for predictive purposes and to refine treatment algorithms.

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades.

Fibrosis is a maladaptive tissue-remodeling process characterized by persistent fibroblast activation, excessive extracellular matrix deposition, and progressive tissue stiffening. Beyond non-neoplastic disorders, fibrosis is also a hallmark of several solid tumors, where it promotes immune evasion, impaired drug delivery, and therapeutic resistance, particularly in pancreatic, hepatocellular, colorectal, and triple-negative breast cancers. In this review, we comparatively analyze fibrosis across non-neoplastic and neoplastic conditions, using idiopathic pulmonary fibrosis as a reference model and comparing it with highly fibrotic tumors. We focus on conserved biological pathways, including TGF-β signaling, ECM remodeling, mechanotransduction, and fibroblast-to-myofibroblast activation, as well as on stromal heterogeneity and the role of cancer-associated fibroblast subsets in tumor progression and immune modulation. We also critically discuss current antifibrotic therapeutic strategies targeting ECM components, fibroblast activation, stromal signaling, and tumor-stroma interactions, highlighting both preclinical rationale and translational limitations. Finally, we examine emerging approaches such as mesenchymal stromal cell-based platforms and drug repurposing strategies bridging oncology and fibrotic diseases. Overall, this review underscores how comparative analysis of cancerous and non-cancerous fibrosis may help identify shared therapeutic vulnerabilities, while supporting the development of context-specific antifibrotic interventions.

Introduction: Mixed adenoneuroendocrine carcinoma (MANEC) is an uncommon and aggressive tumor arising throughout the entire gastrointestinal tract. Treatment options are limited, and survival is dismal with conventional therapies. Case description: We present the case of a 66-year-old man who was diagnosed with a locally advanced MANEC of the gastroesophageal junction. He was treated with perioperative chemotherapy and total gastrectomy. After anastomotic tumor recurrence was detected, he underwent three systemic regimens, including chemoradiotherapy. The patient was then tested for mismatch repair (MMR) protein status, revealing defective expression of MLH1 and PMS2 proteins. Treatment with anti–programmed death 1 (PD-1) receptor monoclonal antibody pembrolizumab was started and radiologic response is ongoing after 11 months. Clinical benefit was evident, and no immune therapy–related side effect was detected. Conclusions: To our knowledge, this is the first report of a heavily pretreated and rapidly progressing deficient MMR gastroesophageal MANEC experiencing a durable benefit from anti-PD1 treatment.

Objective No-visitor policies adopted to prevent coronavirus disease-19 (COVID-19) spread in hospital wards have deeply impacted communication with patients and their relatives. Whereas in pre-COVID-19 era family-clinician meetings were held in person, during the pandemic interactions often took place over the phone, frequently causing feelings of uncertainty and distress to the close ones at home. The goal of this study was to assess and improve the effectiveness of structured telephone-based communication with hospitalized onco-hematological patients’ relatives in COVID-19 era. Methods After no-visitor policy was adopted in the Onco-Hematological Unit of Modena, inpatients’ relatives were contacted daily for clinical updates. After discharge, a telephone satisfaction survey was administered to all contact people of patients consecutive admitted between December 2020 and January 2021 (n = 97). Mean score of response and potential statistically significative differences depending on respondents’ characteristics were assessed. Results Most relatives were satisfied with the communication received with a mean total score of 4.69 on a 5-point Likert scale (standard deviation: 0.60). Results showed high satisfaction rate with both the informative (mean ± SD: 4.66 ± 0.64) and emotional (mean ± SD: 4.66 ± 0.58) content, with no significant difference depending on respondents’ demographic characteristics (p > 0.05). Conclusion A structured telephone-based communication may be a reasonable substitute for face-to-face meetings; especially if regular in time, conducted by the same doctor and integrated with video calls. Our findings might assist health workers in implementing measures to minimize the psychological effects of no-visitor policies during hospitalization. Clinical updates delivery through structured phone calls and video calls could become an opportunity also in post-COVID era.