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Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions of the head and neck, mainly the salivary glands. In general, the primary treatment modality for ACC is surgical resection and, in some cases, postoperative radiotherapy. However, no effective systemic treatment is available for patients with advanced disease. Furthermore, this tumor type is characterized by recurrent molecular alterations, especially rearrangements involving the MYB, MYBL1 , and NFIB genes. In addition, they also reported copy number alterations (CNAs) that impact genes. One of them is C-KIT , mutations that affect signaling pathways such as NOTCH, PI3KCA, and PTEN, as well as alterations in chromatin remodeling genes. The identification of new molecular targets enables the development of specific therapies. Despite ongoing investigations into immunotherapy, tyrosine kinase inhibitors, and anti-angiogenics, no systemic therapy is approved by the FDA for ACC. In this review, we report the genetic and cytogenetic findings on head and neck ACC, highlighting possible targets for therapeutic interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 da Silva, Carvalho de Azevedo, Ralph, Pinheiro, Freitas and Calcagno.)

Primary immunodeficiencies (PID) are rare, complex diseases that can be characterised by a spectrum of phenotypes, from increased susceptibility to infections to autoimmunity, allergy, auto-inflammatory diseases and predisposition to malignancy. With the introduction of genetic testing in these patients and wider use of next-Generation sequencing techniques, a higher number of pathogenic genetic variants and conditions have been identified, allowing the development of new, targeted treatments in PID. The concept of precision medicine, that aims to tailor the medical interventions to each patient, allows to perform more precise diagnosis and more importantly the use of treatments directed to a specific defect, with the objective to cure or achieve long-term remission, minimising the number and type of side effects. This approach takes particular importance in PID, considering the nature of causative defects, disease severity, short- and long-term complications of disease but also of the available treatments, with impact in life-expectancy and quality of life. In this review we revisit how this approach can or is already being implemented in PID and provide a summary of the most relevant treatments applied to specific diseases., Competing Interests: The authors declare that the review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pinto and Neves.)

Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective. Nevertheless, immunocompromised participants were excluded from randomized controlled clinical trials. This study evaluates the efficacy and safety of the Pfizer/BioNTech BNT162b2 (BNT162b2) vaccine in patients with breast and gynecological cancer treated with active anticancer therapy versus a control cohort of healthy participants., Methods: Immune responses to the BNT162b2 vaccine in patients with breast cancer ( n = 44) or a gynecological malignancy ( n = 6) on active anticancer therapy (28 on chemotherapy, mostly anthracycline- or taxane-based, and 22 on target therapy) and in a control cohort of participants without cancer ( n = 67) were investigated by SARS-CoV-2 neutralizing antibody titers measured by S1-binding immunoglobulin G (IgG) concentrations assessed using the LIAISON XL tools (DiaSorin S.p.A.). Response was assessed after a second dose of the BNT162b2 vaccine administered before and at least 3 weeks after the vaccine dose., Results: Overall, 43/50 (86%) patients of the cancer cohort (74% in the breast cancer group and 100% in the gynecological malignancy group) developed IgG antibodies after the second dose of the BNT162b2 vaccine. There were no statistically significant differences in responder rates between patients treated with chemotherapy and those on target therapy. The majority of patients who received chemotherapy with or without target therapy, 21/28 (75%), developed a reliable antibody titer after a vaccine. All seven non-responder patients were undergoing an anthracycline-based regimen. Based on IgG levels (0-400 AU/ml), patients were classified as negative ('non-responders'), weakly positive, or strongly positive ('responders'). No delay in cancer therapy schedule or reported side effects were recorded after BNT162b2 vaccine administration. All healthy participants were strongly positive. Responder rates differed significantly between the two study cohorts (p < 0.001)., Conclusions: Most patients develop antibody titers after the second immunization. However, given the persistence of non-responders or weak responders, additional immunization booster seems to be required, along with proactive planning in the vaccination schedule, with vaccine administration spaced out over time with respect to chemotherapy., Competing Interests: CD reports personal fees from Roche, AstraZeneca, Lilly, GSK, Novartis, Seagen and Pfizer, Advisory Board for Roche, AstraZeneca, Lilly, GSK, Novartis, Seagen and Pfizer, support for attending meetings and/or travel Roche, AstraZeneca, Lilly, GSK, Novartis, Celgene and Pfizer, grants from Novartis. FS received a European Society for Medical Oncology (ESMO) Fellowship -Translational and the 2021 BBVA Foundation/Hospital Clinic of Barcelona Joan Rodés -Jose Baselga Advanced Research Contract in Oncology. MG reports consulting or advisory Role from Lilly, Seagen, Roche, MSD, Gilead, Novartis and Pfizer, Speaker’s Bureau for Lilly, Seagen, AstraZeneca, Novartis and Pfizer, support for attending meetings and/or travel Novartis and Pfizer, Roche, grants from Novartis. RBi is on the Advisory Board for Pfizer, Astrazeneca and Novartis; GA reports personal fees from Novartis, during the conduct of the study; personal fees from Lilly, grants and personal fees from Roche, grants, personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from AstraZeneca, personal fees from Daichi, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer UM declared a shared affiliation with the authors to the handling editor at time of review., (Copyright © 2022 De Placido, Pietroluongo, De Angelis, Tafuro, Barraco, Giannatiempo, Buonaiuto, Schettini, Iervolino, Vozzella, Giuliano, Bianco and Arpino.)

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. Although the diagnostic scheme of HCC is currently undergoing refinement, the prognosis of HCC is still not satisfactory. In addition to certain factors, such as tumor size and number and vascular invasion displayed on traditional imaging, some histopathological features and gene expression parameters are also important for the prognosis of HCC patients. However, most parameters are based on postoperative pathological examinations, which cannot help with preoperative decision-making. As a new field, radiomics extracts high-throughput imaging data from different types of images to build models and predict clinical outcomes noninvasively before surgery, rendering it a powerful aid for making personalized treatment decisions preoperatively., Objective: This study reviewed the workflow of radiomics and the research progress on magnetic resonance imaging (MRI) radiomics in the diagnosis and treatment of HCC., Methods: A literature review was conducted by searching PubMed for search of relevant peer-reviewed articles published from May 2017 to June 2021.The search keywords included HCC, MRI, radiomics, deep learning, artificial intelligence, machine learning, neural network, texture analysis, diagnosis, histopathology, microvascular invasion, surgical resection, radiofrequency, recurrence, relapse, transarterial chemoembolization, targeted therapy, immunotherapy, therapeutic response, and prognosis., Results: Radiomics features on MRI can be used as biomarkers to determine the differential diagnosis, histological grade, microvascular invasion status, gene expression status, local and systemic therapeutic responses, and prognosis of HCC patients., Conclusion: Radiomics is a promising new imaging method. MRI radiomics has high application value in the diagnosis and treatment of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gong, Tao, Wu, Liu, Yu, Wang, Zheng, Liu, Huang, Li, Yang, Wei, Yang and Zhang.)

T-cell acute lymphoblastic leukemia/lymphoma is an aggressive hematological neoplasm whose classification is still based on immunophenotypic findings. Frontline treatment encompass high intensity combination chemotherapy with good overall survival; however, relapsing/refractory patients have very limited options. In the last years, the understanding of molecular physiopathology of this disease, lead to the identification of a subset of patients with peculiar genetic profile, namely "early T-cell precursors" lymphoblastic leukemia, characterized by dismal outcome and indication to frontline allogeneic bone marrow transplant. In general, the most common mutations occur in the NOTCH1/FBXW7 pathway (60% of adult patients), with a positive prognostic impact. Other pathogenic steps encompass transcriptional deregulation of oncogenes/oncosuppressors, cell cycle deregulation, kinase signaling (including IL7R-JAK-STAT pathway, PI3K/AKT/mTOR pathway, RAS/MAPK signaling pathway, ABL1 signaling pathway), epigenetic deregulation, ribosomal dysfunction, and altered expression of oncogenic miRNAs or long non-coding RNA. The insight in the genomic landscape of the disease paves the way to the use of novel targeted drugs that might improve the outcome, particularly in relapse/refractory patients. In this review, we analyse available literature on T-ALL pathogenesis, focusing on molecular aspects of clinical, prognostic, and therapeutic significance., (Copyright © 2020 Fattizzo, Rosa, Giannotta, Baldini and Fracchiolla.)

microRNAs (miRNAs) regulate gene expression by modulating the translation of protein-coding RNAs. Their aberrant expression is involved in various human diseases, including cancer. Here, we summarize the experimental pieces of evidence that proved how dysregulated miRNA expression can lead to RAS (HRAS, KRAS, or NRAS) activation irrespective of their oncogenic mutations. These findings revealed relevant pathogenic mechanisms as well as mechanisms of resistance to target therapies. Based on this knowledge, potential approaches for the control of RAS oncogenic activation can be envisioned., (Copyright © 2019 Roncarati, Lupini, Shankaraiah and Negrini.)

Cancer treatment with either standard chemotherapy or targeted agents often results in the emergence of drug-refractory cell populations, ultimately leading to therapy failure. The biological features of drug resistant cells are largely overlapping with those of cancer stem cells and include heterogeneity, plasticity, self-renewal ability, and tumor-initiating capacity. Moreover, drug resistance is usually characterized by a suppression of proliferation that can manifest as quiescence, dormancy, senescence, or proliferative slowdown. Alterations in key cellular pathways such as autophagy, unfolded protein response or redox signaling, as well as metabolic adaptations also contribute to the establishment of drug resistance, thus representing attractive therapeutic targets. Moreover, a complex interplay of drug resistant cells with the micro/macroenvironment and with the immune system plays a key role in dictating and maintaining the resistant phenotype. Recent studies have challenged traditional views of cancer drug resistance providing innovative perspectives, establishing new connections between drug resistant cells and their environment and indicating unexpected therapeutic strategies. In this review we discuss recent advancements in understanding the mechanisms underlying drug resistance and we report novel targeting agents able to overcome the drug resistant status, with particular focus on strategies directed against dormant cells. Research on drug resistant cancer cells will take us one step forward toward the development of novel treatment approaches and the improvement of relapse-free survival in solid and hematological cancer patients.