Acute lymphoblastic leukemia (ALL) is the most common childhood cancer but is less frequent in adolescents and young adults (AYAs) and is rare among older adults. The 5-year survival of ALL is above 90% in children, but drops significantly in AYAs, and over half of ALL-related deaths occur in older adults. In addition to diagnosis age, the race/ethnicity of patients consistently shows association with ALL incidence and outcomes. Here, we review the racial/ethnic disparities in ALL incidence and outcomes, discuss how these vary across the age spectrum, and examine the potential causes of these disparities. In the United States, the incidence of ALL is highest in Hispanics/Latinos and lowest in Black individuals across all age groups. ALL incidence is rising fastest in Hispanics/Latinos, especially in AYAs. In addition, survival is worse in Hispanic/Latino or Black ALL patients compared to those who are non-Hispanic White. Different molecular subtypes of ALL show heterogeneities in incidence rates and survival outcomes across age groups and race/ethnicity. Several ALL risk variants are associated with genetic ancestry, and demonstrate different risk allele frequencies and/or effect sizes across populations. Moreover, non-genetic factors including socioeconomic status, access to care, and environmental exposures all likely influence the disparities in ALL risk and survival. Further studies are needed to investigate the potential joint effects and interactions of genetic and environmental risk factors. Improving survival in Hispanic/Latino and Black patients with ALL requires advances in precision medicine approaches, improved access to care, and inclusion of more diverse populations in future clinical trials.

Androgen is an important factor in the occurrence and progression of prostate cancer. The principal clinical strategy is androgen deprivation therapy (ADT). However, progression to castrate-resistant prostate cancer (CRPC) is almost inevitable to occur after ADT. One of the key mechanisms is the intertumoral synthesis of androgen where 3β-hydroxysteroid dehydrogenase isoenzyme-1 (3βHSD1, encoded by HSD3B1) catalyzes the rate-limiting step. A germline missense-encoding variant of HSD3B1(1245A>C, rs1047303) has been the focus of research because HSD3B1(1245C) works as an adrenal-permissive allele and encodes a more stable enzyme that promotes the synthesis of androgen. Several studies were performed to explore the role of HSD3B1(1245C) in the development of CRPC and the outcome of clinical management. Thus, we searched the published research articles using the keywords “prostate cancer” and “HSD3B1”, in PubMed and Embase database. After reviewing the abstracts and full articles, 16 original research articles from 45 search results were finally selected and reviewed. Based on the current evidence, HSD3B1(1245C) is proposed to accelerate ADT resistance and the development of CRPC. It is also associated with a poorer prognosis of PCa treated with ADT. However, due to conflicting results, the association between HSD3B1(1245C) and the effect of next-generation hormone therapy (i.e., abiraterone) for patients with CRPC is not clear enough. In conclusion, HSD3B1(1245C) has value for predicting the outcome of PCa and potential to be involved in therapeutic decision making.

Aim: With a need to expand the monitoring options in therapeutic clinical trials, we evaluated the additional information provided by wide-field optical coherence tomography (W-OCT) compared to conventional macular volume scan OCT (M-OCT) in ABCA4 gene-associated inherited retinal dystrophies (ABCA4-IRD).

Methods: A consecutive series of 52 ABCA4-IRD patients (mean age at last examination: 35.9 years, range 8.8-68.7 years) was examined between 2015 and 2021. Ophthalmologic examination included clinical examination, M-OCT [20 × 20 degree field (6.2 mm × 6.2 mm)], W-OCT [55 × 25 degree field (16.1 mm × 7.3 mm)], multicolor reflectance photography, fundus (FAF), and near-infrared autofluorescence (NIA) in macular and wide-field mode. Molecular genetic testing to confirm the clinical phenotype was performed in all patients.

Results: In 37/52 (71.2%) of patients W-OCT revealed alterations of the outer retinal layers beyond the area covered by M-OCT at their last examination. In 15 patients, lesions were located within the area covered by M-OCT. Lesions beyond M-OCT consisted of subretinal material (31/37), as well as patches (18/37) or large continuous areas (3/37) of photoreceptor and retinal pigment epithelial dystrophy. In one patient, W-OCT identified peripheral lesions that were not detectable in wide-field FAF and NIA. In 48/52 patients, two causative mutations in the ABCA4 gene were identified, while the remaining four patients carried one pathogenic ABCA4 variant.

Conclusion: W-OCT as well as wide-field FAF and NIA document lesions in the retinal mid- and far periphery in the majority of ABCA4-IRD patients and provide means for detailed analysis of progression and future treatment planning and monitoring.

Treatment-associated small cell neuroendocrine carcinoma of the prostate (t-SCNC) is an aggressive prostate cancer variant with rising incidence. Although morphologically similar to de novo small cell prostate cancer, t-SCNC is thought to emerge from metastatic castration-resistant prostate cancer (mCRPC) under the selective pressure of prolonged AR-targeted therapies. t-SCNC is associated with a distinct transcriptional landscape, characterized by the upregulation of stem cell-associated and neuronal programs (e.g., SOX2, N-MYC, FOXA2) and decreased canonical AR signaling. In addition, as with other neuroendocrine carcinomas, RB1 loss and inactivating TP53 mutations are key genomic hallmarks of t-SCNC. Nevertheless, despite their histologic, molecular, and clinical differences, there is a striking degree of genomic overlap between t-SCNC and its adenocarcinoma counterpart. This finding underscores the clonal evolution of t-SCNC from mCRPC, as well as the importance of epigenetic mechanisms in regulating tumor phenotype. In this review, we summarize the key genomic, transcriptional, and epigenetic features of t-SCNC and discuss how recent advances in our understanding of molecular drivers of t-SCNC have contributed to improving the diagnosis and treatment of this aggressive disease.

Aim: About a third of patients with autism spectrum disorder (ASD) receive pharmacological treatment for comorbid symptoms. However, 30%-50% do not respond adequately and/or present severe and long-lasting side effects. Previous studies have reported the influence of variants in genes coding for drug targets on the efficacy and safety of pharmacological treatments, including genetic polymorphisms in dopaminergic and serotonergic systems. However, most studies have focused on the adult population, with relatively few studies in children and adolescents, and no clear biomarkers of response have been reported in these populations. The aim of our study was to identify genetic predictors of drug response in patients with ASD. This information may be used to personalise pharmacological treatment and improve the efficacy and safety of psychotropic drugs in patients with ASD.

Methods: Genetic variants in dopaminergic and serotonergic drug targets (SLC6A3, DRD2, DRDRD3, DRD4, HTR2A, and HTR2C) and in other genes previously associated with treatment efficacy and/or induced side effects (ANKK1, BDNF, COMT, and HTR1A) were investigated in 176 children and adolescents diagnosed with ASD and undergoing pharmacological treatment.

Results: A SLC6A3 genetic variant was associated with response to methylphenidate in our ASD cohort, whereas HTR2A and HTR2C allele and haplotype distributions were associated with adverse reactions such as somnolence, mood alterations, and BMI. ANKK1, COMT, and BDNF genetic variants were mainly associated with treatment side effects.

Conclusion: If confirmed, these genetic variants may be used as predictors of clinical outcome and help to personalise pharmacological treatments in patients with ASD.

Aim: We aimed to compare the quantity and quality of aging retinal organoids generated by applying three distinct differentiation protocols for human-derived induced pluripotent stem cells (hiPSC).

Methods: hiPSC were differentiated to retinal organoids using a 3D technique (Method 1) and a 3D-2D-3D technique (Method 2), the latter modified by the addition of BMP4 (Method 3). To investigate the retinal organoid quantity, we counted the number of retinal domains, precursors to organoids during differentiation. The retinal organoid quality was evaluated by immunostaining for markers of different retinal cell types in whole cryosections after days 85, 120, and 200 in culture.

Results: Method 3 produced strikingly more retinal domains per differentiation (65 ± 27) than Methods 1 (12.3 ± 11.2) and 2 (6.3 ± 6.7). Furthermore, retinal organoids differentiated with Method 3 contained significantly more CRX-positive photoreceptors and BRN3A-positive ganglion cells after 85 days in culture, compared to Methods 1 and 2. After 200 days in culture, the retinal organoids differentiated with Method 3 showed proper maturation, as demonstrated by the expression of mature rod and cone photoreceptor markers.

Conclusion: This study demonstrates that the retinal organoid differentiation method can significantly impact the cellular composition of retinal organoids at various time points of development.

Natural killer (NK) cells have a key role in host anti-tumour immune responses via direct killing of tumour cells and promotion of adaptive immune responses. They are therefore attractive targets to promote the anti-tumour efficacy of oncolytic viral therapies. However, NK cells are also potent components of the host anti-viral immune response, and therefore have the potential for detrimental anti-viral responses, limiting the spread and persistence of oncolytic viruses. Oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma (HCC), a leading cause of cancer-related death with a high unmet clinical need. In this review, we highlight the role of NK cells in oncolytic virus therapy, their potential for improving treatment options for patients with HCC, and discuss current and potential strategies targeting NK cells in combination with oncolytic viral therapies.

Extranodal natural killer/T cell lymphoma (NKTCL) is a heterogenous and unique epidemiological non-Hodgkin’s lymphoma, which is strongly associated with Epstein-Barr virus (EBV) infection. Based on the development of various sequencing methods and molecular biology technologies, genome- and transcriptome-wide association studies of NKTCL have provided insight into the etiology and pathogenesis of NKTCL. Comparative genomic hybridization detected variations in tumor suppressor genes such as PRDM1, RUNX3, and EZH2. Whole-exome sequencing identified pathogenic variant such as DDX3X, and TP53. Signal pathways such as the Janus kinase/signal transduction and activator of transcription pathway and nuclear factor kappaB pathway are frequently abnormal in NKTCL. In addition, programmed death-1, programmed death ligand-1, and the human leukocyte antigen risk alleles are significantly associated with NKTCL pathogenesis. Meanwhile, epigenetics analysis has also exposited changes such as PTPRK, HACE1, microRNAs, and long non-coding RNAs, which play important role on the development and biology of NKTCL. EBV infection is tightly correlated with NKTCL. Viral genomic alterations and lytic genes of EBV are reported to have pathogenic effects on host cells that contribute to the etiology of NKTCL. We summarize the genomic and genetic alterations during the pathogenesis and development of NKTCL and exhibit the potential therapeutic targets that are worth exploring in future research and clinical trials.

Prostate cancer (PCa) is the most commonly diagnosed malignancy among men, and the progression of this disease results in fewer treatment options available to clinical patients. It highlights the vital necessity for discovering novel therapeutic approaches and expanding the current understanding of molecular mechanisms. Epigenetic alternations such as DNA methylation models and histone modifications have been associated as key drivers in the development and advancement of PCa. Several studies have been conducted and demonstrated that targeting these epigenetic enzymes or regulatory proteins has been strongly associated with the regulation of cancer cell growth. Due to the success rate of these therapeutic routes in pre-clinical settings, many drugs have now advanced to clinical testing, where efficacy will be measured. This review will discuss the role of epigenetic modifications in PCa development and its function in the progression of the disease to resistant forms and introduce therapeutic strategies that have demonstrated successful results as PCa treatment.