IMPs, also known as insulin-like growth factor 2 (IGF2) messenger RNA (mRNA)-binding proteins (IGF2BPs), are highly conserved oncofetal RNA-binding proteins (RBPs) that regulate RNA processing at several levels, including localization, translation, and stability. Three mammalian IMP paralogs (IMP1–3) have been identified that are expressed in most organs during embryogenesis, where they are believed to play an important role in cell migration, metabolism, and stem cell renewal. Whereas some IMP2 expression is retained in several adult mouse organs, IMP1 and IMP3 are either absent or expressed at very low levels in most tissues after birth. However, all three paralogs can be re-expressed upon malignant transformation and are found in a broad range of cancer types where their expression often correlates with poor prognosis. IMPs appear to resume their physiological functions in malignant cells, which not only contribute to tumor progression but participate in the establishment and maintenance of tumor cell hierarchies. This review summarizes our current understanding of the functions of IMPs during normal development and focuses on a series of recent observations that have provided new insight into how their physiological functions enable IMPs to play a potentially key role in cancer stem cell maintenance and tumor growth.

Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing. Using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we show that insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) binds to let-7 miRNA recognition elements (MREs) and prevents let-7 target gene silencing. Our observations define the RNA-binding repertoire of IMP2 and identify a mechanism whereby it supports GSC and neural stem cell specification.

Immune checkpoint inhibitors (ICIs) and BRAF and MEK inhibitors (BRAFi/MEKi) have drastically improved the outcome of melanoma patients. ICIs can induce myocarditis, a rare immune related adverse event (irAE) with an estimated lethality of 50%. BRAFi/MEKi may induce left ventricular ejection fraction decrease, hypertension or QT interval prolongation. While the BRAFi/MEKi induced cardiotoxicity is often reversible upon treatment discontinuation or dose adaptation and symptomatic therapy is often sufficient to restore cardiac function, the treatment of ICI-induced myocarditis mainly relies on high dose corticosteroids. There is no established therapy for steroid resistant myocarditis, yet various drugs have been reported to improve outcome. Shared epitopes between melanoma cells and cardiac tissue are thought to underlie the development of ICIs induced myocarditis. The mechanism of BRAFi/MEKi induced cardiotoxicity appears to be related to the Ras-Raf-MEK-ERK pathway in cardiomyocyte repair, survival and proliferation. With the emerging application of ICI-BRAFi/MEKi combinations, so called triplet therapies, differentiating between these two types of cardiotoxicity will become important for appropriate patient management.In this article we provide a summary of the existing literature on the pathophysiology, diagnosis and management of cardiotoxicity of melanoma therapies.

Medullary thyroid cancer (MTC) represents an aggressive form of thyroid malignancy. Some may occur spontaneously or can be associated with Multiple Endocrine Neoplasia syndromes, or Familial Medullary Thyroid Cancer syndrome. In these patients, the protooncogene RET (rearranged during transfection) is mutated. In patients who have unresectable or metastatic disease, the long term prognosis is poor. New treatments for this disease have focused on the use of targeted agents that inhibit the receptor tyrosine kinase of RET. One of these treatments, Vandetanib (Caprelsa, Astra Zeneca), recently has received approval from the Food and Drug Administration for the treatment of patients with progressive locally advanced and/or metastatic disease. This review highlights the studies that led to the drug’s approval, and discusses on the potential financial costs of treatment and side effects of this therapy. The main clinical studies evaluating Vandetanib for the treatment of other solid tumors will also be reviewed.

We are continuously progressing in our understanding of cancer and other diseases and learned how they can be heterogeneous among patients. Therefore, there is an increasing need for accurate characterization of diseases at the molecular level. In parallel, medical imaging and image-guided therapies are rapidly developing fields with new interventions and procedures entering constantly in clinical practice. Theranostics, a relatively new branch of medicine, refers to procedures combining diagnosis and treatment, often based on patient and disease-specific features or molecular markers. Interventional oncology which is at the convergence point of diagnosis and treatment employs several methods related to theranostics to provide minimally invasive procedures tailored to the patient characteristics. The aim is to develop more personalized procedures able to identify cancer cells, selectively reach and treat them, and to assess drug delivery and uptake in real-time in order to perform adjustments in the treatment being delivered based on obtained procedure feedback and ultimately predict response. Here, we review several interventional oncology procedures referring to the field of theranostics, and describe innovative methods that are under development as well as future directions in the field.

Purpose: Hepatic and/or portal vein embolization are performed before hepatectomy for patients with insufficient future liver remnant and usually achieved with a trans-hepatic approach. The aim of the present study is to describe a modified trans-venous liver venous deprivation technique (mLVD), avoiding the potential risks and limitations of a percutaneous approach to hepatic vein embolization, and to assess the safety, efficacy, and surgical outcome after mLVD.Materials and Methods: Retrospective single-center institutional review board-approved study. From March 2016 to June 2019, consecutive oncologic patients with combined portal and hepatic vein embolization were included. CT volumetric analysis was performed before and after mLVD to assess liver hypertrophy. Complications related to mLVD and surgical outcome were obtained from medical records.Results: Thirty patients (62.7 ± 14.5 years old, 20 men) with liver metastasis (60%) or primary liver cancer (40%) underwent mLVD. Twenty-one patients (70%) had hepatic vein anatomic variants. Technical success of mLVD was 100%. Four patients had complications (three minor and one major). FLR hypertrophy was 64.2% ± 51.3% (mean ± SD). Twenty-four patients (80%) underwent the planned hepatectomy and no surgery was canceled as a consequence of mLVD complications or insufficient hypertrophy. Fifty percent of patients (12/24) had no or mild complications after surgery (Clavien-Dindo 0–II), and 45.8% (11/24) had more serious complications (Clavien-Dindo III–IV). Thirty-day mortality was 4.2% (1/24).Conclusion: mLVD is an effective method to induce FLR hypertrophy. This technique is applicable in a wide range of oncologic situations and in patients with complex right liver vein anatomy.

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Le cancer pulmonaire à petites cellules (CPPC) est une tumeur récalcitrante avec une survie à 5 ans de moins de 20 %. Il est fréquemment découvert à un stade métastatique malgré le nouveau dépistage par computed tomography scan low-dose. Le séquençage à haut débit a permis d'approfondir notre compréhension de sa biologie. Bien que le traitement du CPPC localisé ait peu évolué, l'immunothérapie par inhibiteurs des points de contrôle a révolutionné la prise en charge de la maladie métastatique. Parallèlement, de nouvelles stratégies impliquant certaines cibles génétiques potentielles sont en cours d'évaluation et pourraient se révéler précieuses à l'avenir. La radiothérapie reste très utile à tous les stades de la maladie. Cet article passe en revue l'épidémiologie, la pathologie moléculaire, la prise en charge et les thérapies novatrices dans le CPPC. Small-cell lung cancer: management and noveltiesSmall cell lung cancer is a recalcitrant malignancy with 5-year survival rates of less than 20%. In the majority of cases, patients have metastatic disease at diagnosis despite the new screening method by low-dose CT-scan. The high throughput sequencing has deepened our understanding of its biology. While the treatment of localized disease has changed little, the arrival of immune checkpoint inhibitors have revolutionized the management of extensive disease. At the same time, new strategies involving certain potential genetic targets are being analyzed on a large scale that could become valuable therapeutic alternatives in the future. Radiation therapy remains a very useful therapeutic modality in all stages of the disease. This article aims to review the epidemiology, molecular pathology, management and innovative therapies in small-cell lung cancer.