DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies to enhance immune responsiveness. Recent research explores combining DNA-damaging therapies with immunotherapy to activate the STING pathway and improve the antitumor immune response.

BRAFV600E mutant metastatic colorectal cancer: Current advances in personalized treatment and future perspectives.

Detection of the BRAF V600E mutation has important genetic, prognostic, and therapeutic implications for patients with metastatic colorectal cancer (mCRC), identifying a subgroup of patients who derive modest benefit from standard treatments and have extremely poor prognosis. The evolution of molecular profiling and the implementation of next generation sequencing in the evaluation of a patient with BRAF-mutated mCRC has currently led to the discovery of actionable alterations. Targeting multiple pathways of resistance in BRAF-mutated mCRC may be the most efficacious route.

Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma.

Purpose: Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.

Experimental Design: In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.

High Incidence of Isolated Tumor Cells in Sentinel Node Biopsies of Thin Melanomas: A Potential Factor in the Paradoxical Prognosis of Stage IIIA Cutaneous Melanoma?

: This study aims to evaluate whether the presence of isolated tumor cells (ITCs) correlates with specific stages of cutaneous melanoma, potentially shedding light on their prognostic significance and the paradoxical survival outcomes in stage IIIA. : This study analyzed cases of sentinel lymph node biopsies for cutaneous melanoma between 2021 and 2023. It included patients with CM diagnoses, available histological slides, and clinical information about the neoplasia stage.

Retrospective-Prospective Observational Study of Italian Patients Treated in Melanoma Adjuvant Cohort MAP-MADAM (Maximing ADjuvAnt MAP): Interim Analysis.

: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. : The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective-prospective observational study that included patients who received at least one dose of D + T through the MAP.

Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach.

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous studies have been conducted on ICIs in other earlier disease settings, including studies conducted in patients in neoadjuvant settings.

Endometrial cancer in the elderly: Characteristics, prognostic and risk factors, and treatment options.

Endometrial cancer incidence and related mortality are on the rise due to aging demographics. This population often presents with unfavorable features, such as myometrial invasion, non-endometrioid histology, high-grade tumors, worse prognosis, etc. The role of age as an independent prognostic factor is still debated, and screening tools addressing frailty emerge as pivotal in guiding treatment decisions; however, they are still underutilized.

Comprehensive genomic profiling by liquid biopsy captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAF wild-type metastatic colorectal cancer in the CAPRI 2-GOIM trial.

Background: Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available.

Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma.

Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed.

Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial.

Background: CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC).

Objective: We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM).

Patients And Methods: Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included.

Targeting the EGFR signalling pathway in metastatic colorectal cancer.

Epidermal growth factor receptor (EGFR) and its activated downstream signalling pathways play a crucial role in colorectal cancer development and progression. After four decades of preclinical, translational, and clinical research, it has been shown that blocking the EGFR signalling pathway at different molecular levels represents a fundamental therapeutic strategy for patients with metastatic colorectal cancer. Nevertheless, the efficacy of molecularly targeted therapies is inescapably limited by the insurgence of mechanisms of acquired cancer cell resistance.

All for one: Collaboration between dermatologist, radiation oncologist and radiologist in the clinical management of "difficult to treat" non melanoma skin cancer.

This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning.

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review.

Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect.

The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients.

Oral Adverse Events Associated with BRAF and MEK Inhibitors in Melanoma Treatment: A Narrative Literature Review.

Background: Melanoma cancer represents the most lethal type of skin cancer originating from the malignant transformation of melanocyte cells. Almost 50% of melanomas show the activation of BRAF mutations. The identification and characterization of BRAF mutations led to the development of specific drugs that radically changed the therapeutic approach to melanoma.

Characteristics of Real-World Patients with High-Risk -Mutated Melanoma Receiving Adjuvant Treatment with Dabrafenib Plus Trametinib After Surgical Resection, Through the Italian Managed Access Program.

Purpose: Real-world data from patients with -mutated, resected, stage III melanoma treated with dabrafenib plus trametinib as adjuvant targeted therapy are limited, and it is important to gain an understanding of the characteristics of this patient population, as well as of the patient journey. Here we aimed to describe the characteristics, dosage reductions and discontinuations in patients with -mutated melanoma receiving adjuvant dabrafenib plus trametinib after surgical resection through an Italian managed access program (MAP).

Patients And Methods: Eligible patients had completely resected cutaneous melanoma with confirmed V600E or V600K mutation, or initially resectable lymph node recurrence after a diagnosis of stage I or II melanoma.

Combined blockade of mTOR and p21-activated kinases pathways prevents tumour growth in KRAS-mutated colorectal cancer.

Background: The identification of novel therapeutic strategies for metastatic colorectal cancer (mCRC) patients harbouring KRAS mutations represents an unmet clinical need. In this study, we aimed to clarify the role of p21-activated kinases (Paks) as therapeutic target for KRAS-mutated CRC.

Methods: Paks expression and activation levels were evaluated in a cohort of KRAS-WT or -mutated CRC patients by immunohistochemistry.

Italian nivolumab Expanded Access Programme in melanoma adjuvant setting: patient outcomes and safety profile.

Introduction: The CheckMate 238 randomised study demonstrated the relevant benefit in terms of recurrence-free survival (RFS) of nivolumab versus ipilimumab in resected stage IIIB-C or IV melanoma patients with a tolerable safety profile.

Materials And Methods: From November 2018 to June 2019, 611 patients with stage III and IV resected melanoma were enroled to receive nivolumab as part of an Italian Expanded Access Programme (EAP). According to stages, 77% were stage III while 141 (23%) were stage IV with no evidence of disease (NED).