A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. HCC tumor development and treatment resistance are impacted by changes in the microenvironment of the hepatic immune system. Immunotherapy has the potential to improve response rates by overcoming immune tolerance mechanisms and strengthening anti-tumor activity in the tumor microenvironment. In this review, we characterize the impact of immunotherapy on outcomes of advanced HCC, as well as the active clinical trials evaluating novel combination immunotherapy strategies. In particular, we discuss the efficacy of atezolizumab and bevacizumab as demonstrated in the IMbrave150 study, which created a new standard of care for the front-line treatment of advanced HCC. However, there are multiple ongoing trials that may present additional front-line treatment options depending on their efficacy/toxicity results. Furthermore, the preliminary data on the application of chimeric antigen receptor (CAR-T) cell therapy for treatment of HCC suggests this may be a promising option for the future of advanced HCC treatment.

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The treatment of advanced gastrointestinal (GI) cancers has become increasingly molecularly driven. Molecular profiling for HER2 and PD-L1 status is standard for metastatic gastroesophageal (GEJ) cancers to predict benefits from trastuzumab (HER2-targeted therapy) and pembrolizumab (anti-PD-1 therapy), while extended RAS and BRAF testing is standard in metastatic colorectal cancer to predict benefits from epidermal growth factor receptor (EGFR)-targeted therapies. Mismatch repair (MMR) or microsatellite instability (MSI) testing is standard for all advanced GI cancers to predict benefits from pembrolizumab and in metastatic colorectal cancer, nivolumab with or without ipilimumab. Here we review recent seminal trials that have further advanced targeted therapies in these cancers including Poly (adenosine diphosphate–ribose) polymerases (PARP) inhibition in pancreas cancer, BRAF inhibition in colon cancer, and isocitrate dehydrogenase (IDH) and fibroblast growth factor receptor (FGFR) inhibition in biliary tract cancer. Targeted therapies in GI malignancies constitute an integral component of the treatment paradigm in these advanced cancers and have widely established the need for standard molecular profiling to identify candidates.

Background Curative-intent treatment of acute myeloid leukaemia (AML) can lead to multiple chronic medical conditions (‘late effects’). Little is known about the burden of late effects in adolescent and young adult (AYA, 15–39 years) survivors of AML. We aimed to estimate the cumulative incidence and investigate the main predictors of late effects among these patients. Methods During 1996–2012, 1168 eligible AYAs with AML who survived ≥2 years after diagnosis were identified in the California Cancer Registry. Late effects were reported from State hospital discharge data, and patients were followed through 2014. Hazard ratios and 95% confidence intervals of late effects occurrence were estimated using Cox proportional hazard models, adjusted for sociodemographic and clinical factors. Results The most common late effects at 10 years after diagnosis were: endocrine (26.1%), cardiovascular (18.6%) and respiratory (6.6%), followed by neurologic (4.9%), liver/pancreatic (4.3%), renal (3.1%), avascular necrosis (2.7%) and second primary malignancies (2.4%). Of 1168 survivors, 547 (46.8%) received a haematopoietic stem cell transplant (HSCT). After multivariable adjustments, AYAs who underwent HSCT or had a non-favourable risk AML experienced ∼2-fold or higher increased likelihood of all late effects. Additionally, AYAs of Hispanic, Black or Asian/Pacific Islander (vs non-Hispanic White) race/ethnicity and those who resided in lower socio-economic neighbourhoods were at higher risk of numerous late effects. Conclusions Our findings underscore the need for long-term surveillance for the prevention, early detection and treatment of late effects, and can inform the development of AYA-focused consensus-based guidelines that will ultimately improve the quality of life and survival of these young vulnerable patients.