Personalized Systemic Therapies in Hereditary Cancer Syndromes

Mastrodomenico, Luciana; Piombino, Claudia; Riccò, B.; Barbieri, Elena; Venturelli, Marta; Piacentini, Federico; Dominici, Massimo; Cortesi, Laura; Toss, Angela

doi:10.3390/genes14030684

Cited by 8 publications

(4 citation statements)

References 210 publications

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“…Individuals carrying a germline variant are at an increased risk of developing cancer. Information on the genetic risk of an individual is useful for personal risk identification, not only for the affected individual but also for the preventive management of family members [32].…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand

Sukpan,

Sangkhathat,

Sriplung

et al. 2023

JPM

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Germline carriers of pathogenic variants in cancer susceptibility genes are at an increased risk of breast cancer (BC). We characterized germline variants in a cohort of 151 patients diagnosed with epithelial BC in the southernmost region of Thailand, where the predominant ethnicity differs from that of the rest of the country. Whole exome sequencing was used to identify and subsequently filter variants present in 26 genes known to be associated with cancer predisposition. Of the 151 individuals assessed, 23, corresponding to 15.2% of the sample, exhibited the presence of one or more pathogenic or likely pathogenic variants associated with BC susceptibility. We identified novel germline truncating variants in BRIP1, CHEK2, MSH6, PALB2, and PTEN and annotated variants of uncertain significance (VUSs), both novel and previously documented. Therefore, it is advisable to use genetic testing as an additional risk screening method for BC in this area.

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Section: Discussionmentioning

confidence: 99%

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand

Sukpan,

Sangkhathat,

Sriplung

et al. 2023

JPM

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“…The information gained from the use of standard gene panel testing and/or NGS to assess both germline and tumor somatic mutations can be leveraged to guide therapy, as in the case of BRCA1/2 mutations and PARP inhibitors. 59 This information can also be used to inform strategies designed to prevent cancer, such as prophylactic total gastrectomy in individuals with germline mutations of CDH1 60 and risk-reducing mastectomy and/or oophorectomy in individuals with germline mutations of BRCA1/2 . 61 There is increasing interest in defining germline modifiers of the immune TME that drive cancer risk and modulate response to immunotherapy in patients with cancer.…”

Section: An Update To the Challenges And Opportunities In Cancer Immu...mentioning

confidence: 99%

Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision

Emens,

Romero,

Anderson

et al. 2024

J Immunother Cancer

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Cancer immunotherapy has flourished over the last 10–15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor microenvironment. With this rapid clinical and scientific progress, the field of cancer immunotherapy is currently at a critical inflection point, with potential for exponential growth over the next decade. Recognizing this, the Society for Immunotherapy of Cancer convened a diverse group of experts in cancer immunotherapy representing academia, the pharmaceutical and biotechnology industries, patient advocacy, and the regulatory community to identify current opportunities and challenges with the goal of prioritizing areas with the highest potential for clinical impact. The consensus group identified seven high-priority areas of current opportunity for the field: mechanisms of antitumor activity and toxicity; mechanisms of drug resistance; biomarkers and biospecimens; unique aspects of novel therapeutics; host and environmental interactions; premalignant immunity, immune interception, and immunoprevention; and clinical trial design, endpoints, and conduct. Additionally, potential roadblocks to progress were discussed, and several topics were identified as cross-cutting tools for optimization, each with potential to impact multiple scientific priority areas. These cross-cutting tools include preclinical models, data curation and sharing, biopsies and biospecimens, diversification of funding sources, definitions and standards, and patient engagement. Finally, three key guiding principles were identified that will both optimize and maximize progress in the field. These include engaging the patient community; cultivating diversity, equity, inclusion, and accessibility; and leveraging the power of artificial intelligence to accelerate progress. Here, we present the outcomes of these discussions as a strategic vision to galvanize the field for the next decade of exponential progress in cancer immunotherapy.

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“…MSI-CRC can be caused by hereditary germline mutations occurring in the MMR genes (MLH1, MSH2, MSH6, and PMS2) and tumor somatic hypermethylation of MLH1. Nearly 10% of CRCs are caused by MLH1 promoter hypermethylation and are often in association with the BRAF V600E pathogenetic variant in sporadic CRC [ 98 ]; CpG island methylator phenotype (CIMP) pathways. In some cases, CRC may be caused by the hypermethylation of promoter CpG island sites, resulting in the silencing of suppressor genes.…”

Section: Molecular Signaturesmentioning

confidence: 99%

Section: Molecular Signaturesmentioning

confidence: 99%

Early Onset Metastatic Colorectal Cancer: Current Insights and Clinical Management of a Rising Condition

Medici,

Riccò,

Caffari

et al. 2023

Cancers

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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.

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Personalized Systemic Therapies in Hereditary Cancer Syndromes

Cited by 8 publications

References 210 publications

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand

Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision

Early Onset Metastatic Colorectal Cancer: Current Insights and Clinical Management of a Rising Condition

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