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Mini Review
20 February 2023
ARID1A in cancer: Friend or foe?
Beatrice Fontana
4 more and 
Manuela Ferracin
(A) Histogram showing ARID1A alteration frequency in 153.554 samples from the AACR GENIE project (39) and the alteration type across human cancers (minimum frequency cutoff at 5%). (B) Type, frequency and distribution of ARID1A mutations on the gene coding sequence across all AACR GENIE project tumor types.

ARID1A belongs to a class of chromatin regulatory proteins that function by maintaining accessibility at most promoters and enhancers, thereby regulating gene expression. The high frequency of ARID1A alterations in human cancers has highlighted its significance in tumorigenesis. The precise role of ARID1A in cancer is highly variable since ARID1A alterations can have a tumor suppressive or oncogenic role, depending on the tumor type and context. ARID1A is mutated in about 10% of all tumor types including endometrial, bladder, gastric, liver, biliopancreatic cancer, some ovarian cancer subtypes, and the extremely aggressive cancers of unknown primary. Its loss is generally associated with disease progression more often than onset. In some cancers, ARID1A loss is associated with worse prognostic features, thus supporting a major tumor suppressive role. However, some exceptions have been reported. Thus, the association of ARID1A genetic alterations with patient prognosis is controversial. However, ARID1A loss of function is considered conducive for the use of inhibitory drugs which are based on synthetic lethality mechanisms. In this review we summarize the current knowledge on the role of ARID1A as tumor suppressor or oncogene in different tumor types and discuss the strategies for treating ARID1A mutated cancers.

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Review
27 July 2022

The need for efficacious and non-toxic cancer therapies is paramount. Oncolytic viruses (OVs) are showing great promise and are introducing new possibilities in cancer treatment with their ability to selectively infect tumor cells and trigger antitumor immune responses. Herpes Simplex Virus 1 (HSV-1) is a commonly selected OV candidate due to its large genome, relative safety profile, and ability to infect a variety of cell types. Talimogene laherparevec (T-VEC) is an HSV-1-derived OV variant and the first and only OV therapy currently approved for clinical use by the United States Food and Drug Administration (FDA). This review provides a concise description of HSV-1 as an OV candidate and the genomic organization of T-VEC. Furthermore, this review focuses on the advantages and limitations in the use of T-VEC compared to other HSV-1 OV variants currently in clinical trials. In addition, approaches for future directions of HSV-1 OVs as cancer therapy is discussed.

3,995 views
16 citations
Mini Review
15 July 2022

The human skin hosts millions of bacteria, fungi, archaea, and viruses. These skin microbes play a crucial role in human immunological and physiological functions, as well as the development of skin diseases, including cancer when the balance between skin commensals and pathogens is interrupted. Due to the linkages between inflammation processes and skin microbes, and viral links to skin cancer, new theories have supported the role a dysbiotic skin microbiome plays in the development of cancer and cancer treatment-related skin toxicities. This review focuses on the skin microbiome and its role in cancer treatment-related skin toxicities, particularly from chemotherapy, radiation therapy, and immunotherapy. The current literature found changes in the diversity and abundance of the skin microbiome during cancer treatments such as radiation therapy, including lower diversity of the skin microbiome, an increased Proteobacteria/Firmicutes ratio, and a higher abundance of pathogenic Staphylococcus aureus. These changes may be associated with the development and severity of treatment-related skin toxicities, such as acute radiation dermatitis, hand-foot syndrome in chemotherapy, and immunotherapy-induced rash. Several clinical guidelines have issued potential interventions (e.g., use of topical corticosteroids, phototherapy, and non-pharmaceutical skin care products) to prevent and treat skin toxicities. The effectiveness of these promising interventions in alleviating treatment-related skin toxicities should be further tested among cancer patients.

4,328 views
18 citations

Metastasis is the primary cause of death in patients with colorectal cancer (CRC), urging the need for preclinical models that recapitulate the metastatic process at the individual patient level. We used an orthotopic patient-derived xenograft (PDX) obtained through the direct implantation of freshly dissociated CRC cells in the colon of immunocompromised mice to model the metastatic process. Ortho-PDX engraftment was associated to a specific set of molecular features of the parental tumor, such as epithelial-to-mesenchymal transition (EMT), TGF-β pathway activation, increased expression of stemness-associated factors and higher numbers of circulating tumor cells (CTCs) clusters expressing the metastatic marker CD44v6. A parallel analysis of orthotopic/metastatic xenografts and organoids showed that tumor cells underwent mesenchymal-to-epithelial transition at the metastatic site and that metastasis-derived organoids had increased chemotherapy resistance. These observations support the usefulness of ortho-PDX as a preclinical model to study metastasis-related features and provide preliminary evidence that EMT/stemness properties of primary colorectal tumors may be crucial for orthotopic tumor engraftment.

4,360 views
14 citations
1 as indicated by the color codes. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.
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11 citations
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Review
24 May 2022

Chemotherapy resistance and peculiar tumor microenvironment, which diminish or mitigate the effects of therapies, make pancreatic cancer one of the deadliest malignancies to manage and treat. Advanced immunotherapies are under consideration intending to ameliorate the overall patient survival rate in pancreatic cancer. Oncolytic viruses therapy is a new type of immunotherapy in which a virus after infecting and lysis the cancer cell induces/activates patients’ immune response by releasing tumor antigen in the blood. The current review covers the pathways and molecular ablation that take place in pancreatic cancer cells. It also unfolds the extensive preclinical and clinical trial studies of oncolytic viruses performed and/or undergoing to design an efficacious therapy against pancreatic cancer.

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8 citations
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