Cervical cancer is the fourth most common cancer in women. Advanced stage and metastatic disease are often associated with poor clinical outcomes. This substantiates the absolute necessity for high-throughput diagnostic and treatment platforms that are patient and tumour specific. Cervical cancer treatment constitutes multimodal intervention. Systemic treatments such as chemotherapy and/or focal radiotherapy are typically applied as neoadjuvant and/or adjuvant strategies. Cisplatin constitutes an integral part of standard cervical cancer treatment approaches. However, despite initial patient response, de novo or delayed/acquired treatment resistance is often reported, and toxicity is of concern. Chemotherapy resistance is associated with major alterations in genomic, metabolomic, epigenetic and proteomic landscapes. This results in imbalanced homeostasis associated with pro-oncogenic and proliferative survival, anti-apoptotic benefits, and enhanced DNA damage repair processes. Although significant developments in cancer diagnoses and treatment have been made over the last two decades, drug resistance remains a major obstacle to overcome.
Despite advances in treatment, the disease’s advanced stages and spread to other parts of the body often lead to poor outcomes. This highlights the urgent need for better diagnostic and treatment methods tailored to each patient and their specific tumour. Treatment for cervical cancer usually involves a combination of therapies. Chemotherapy and focused radiation therapy are commonly used before or after surgery to improve outcomes. However, some patients develop resistance to these treatments, either from the start or after initially responding to therapy. This resistance can make treatment less effective and increase the risk of side effects. Chemotherapy resistance is often linked to changes in the genes and proteins of cancer cells. These changes disrupt the normal balance within the cells, making them more prone to grow and survive, resist cell death, and repair DNA damage caused by treatment. Despite progress in cancer research and treatment, drug resistance remains a significant challenge. This review aims to explore how acquired genetic mutations contribute to drug resistance in cervical cancer. By understanding these mutations better, researchers and clinicians in low- to middle-income countries can develop more effective treatment strategies to improve outcomes for patients.

Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

OBJECTIVE: The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events.
METHODS: Embase, Cochrane, Scopus, and Web of Science.
METHODS: The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Databases were searched from inception through May 23, 2023.
RESULTS: A total of 42 studies met inclusion criteria. Twenty-four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6-8.6), 18.9% (95% CI: 18.1-19.8), and 8.5% (95% CI: 8.1-9.0) of reported patients were positive for BRAF, NRAS, and KIT mutations, respectively. The presence of brisk tumor-infiltrating lymphocytes was associated with improved recurrence-free survival and overall survival (OS). Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8-43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI\'s.
CONCLUSIONS: ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease.

The majority of our hereditary breast cancer genes incur not only an increased risk for breast cancer but for other malignancies as well. Knowing whether an individual carries a pathogenic variant in a hereditary breast cancer gene can affect not only screening for the patient but for his or her family members as well. Identifying and appropriately testing individuals via multigene panels allows for risk reduction and early surveillance in at-risk individuals. Radiologists can serve as first-line identifiers of women who are at risk of having an inherited predisposition to breast cancer because they are interacting with all women receiving routine screening mammograms, and collecting family history suggestive of the presence of a mutation. We outline here the 11 genes associated with high breast cancer risk discussed in the National Comprehensive Cancer Network Genetic/Familial High-Risk: Breast and Ovarian (version 3.2019) as having additional breast cancer screening recommendations outside of annual mammography to serve as a guide for breast cancer screening and risk reduction, as well as recommendations for surveillance of nonbreast cancers.

Generalized pustular rashes have various etiologies and can be challenging to diagnose and manage at first presentation. The authors provide an in-depth analysis of common pustular skin eruptions including generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis, focusing on their pathophysiology, triggers, clinical presentation, diagnostic challenges, and management strategies. The article also highlights recent advances in genetic research and biologic therapies for GPP and the future directions in personalized medicine and prevention strategies.

The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.

Cardiac tumours can occur in association with genetic syndromes. Rhabdomyomas have been reported in association with tuberous sclerosis, myxomas with Carney\'s complex, cardiac fibromas with Gorlin syndrome, and paragangliomas with multiple endocrine neoplasm syndrome. The presentation and prognosis of cardiac tumours associated with genetic syndromes differ compared with sporadic cases. Knowledge about the associated syndromes\' genetic features and extracardiac manifestations is essential for the diagnosis, prognosis, and management of cardiac neoplasms. Moreover, identifying genetic mutations in benign and malignant cardiac tumours is needed to personalise management and improve treatment outcomes. Thus, this review discusses the genetic abnormalities associated with cardiac tumours, the current genetic screening recommendations, and the effect of those genetic mutations on the outcomes.

Cutaneous melanoma (CM) is an increasingly significant public health concern. Due to alarming mortality rates and escalating incidence, it is crucial to understand its etiology and identify emerging biomarkers for improved diagnosis and treatment strategies. This review aims to provide a comprehensive overview of the multifactorial etiology of CM, underscore the importance of early detection, discuss the molecular mechanisms behind melanoma development and progression, and shed light on the role of the potential biomarkers in diagnosis and treatment. The pathogenesis of CM involves a complex interplay of genetic predispositions and environmental exposures, ultraviolet radiation exposure being the predominant environmental risk factor. The emergence of new biomarkers, such as novel immunohistochemical markers, gene mutation analysis, microRNA, and exosome protein expressions, holds promise for improved early detection, and prognostic and personalized therapeutic strategies.

Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.

Arrhythmogenic cardiomyopathy (ACM) is a myocardium disease characterized by phenotypic features of myocardial scarring due to fibrofatty myocardial replacement often associated with global or regional ventricular dysfunction. For years after arrhythmogenic right ventricular cardiomyopathy (ARVC) was first described, the left ventricle (LV) was generally considered normal or minimally involved. In recent years, however, LV involvement has been recognized. It usually presents with early-on arrhythmias more than heart failure symptoms compared to dilated cardiomyopathy. It can be right ventricular, biventricular, or left ventricular. The underlying pathophysiology involves either desmosomal or non-desmosomal mutations. Phospholamban (PLN) mutation is one of those and is associated with more severe arrhythmias and SCD. Primary prevention with ICD implantation should be considered in these patients, even the ones with an ejection fraction greater than 35%. In addition, if such patients progress to Stage D heart failure, they need to be evaluated for advanced heart failure therapies.