The role of epigenetic therapies in colorectal cancer

Although developments in the diagnosis and therapy of colorectal cancer (CRC) have been made in the last decade, much work remains to be done as it remains the second leading cause of cancer death. It is now well established that epigenetic events, together with genetic alterations, are key events in initiation and progression of CRC. Epigenetics refers to heritable alterations in gene expression that do not involve changes in the DNA sequence. These alterations include DNA methylation, histone alterations, chromatin remodelers, and noncoding RNAs. In CRC, aberrations in epigenome may also involve in the development of drug resistance to conventional drugs such as 5-fluorouracil, oxaliplatin, and irinotecan. Thus, it has been suggested that combined therapies with epigenetic agents may reverse drug resistance. In this regard, DNA methyltransferase inhibitors and histone deacetylase inhibitors have been extensively investigated in CRC. The aim of this review is to provide a brief overview of the preclinical data that represent a proof of principle for the employment of epigenetic agents in CRC with a focus on the advantages of combinatorial therapy over single-drug treatment. We will also critically discuss the results and limitations of initial clinical experiences of epigenetic-based therapy in CRC and summarize ongoing clinical trials. Nevertheless, since recent translational research suggest that epigenetic modulators play a key role in augmenting immunogenicity of the tumor microenvironment and in restoring immune recognition, we will also highlight the recent developments of combinations strategies of immunotherapies and epigenetic therapies in CRC, summarizing preclinical, and clinical data to signify this evolving and promising field for CRC treatment.     

鼻咽癌免疫治疗进展

鼻咽癌是一种与EB病毒(EBV)感染密切相关的恶性肿瘤。鼻咽癌在接受现代调强放疗技术为主的综合治疗后,疗效得到进一步提高。提高高危患者和复发/远处转移鼻咽癌(R/M-NPC)患者的疗效成为治疗的主要目标。近年来,免疫治疗在肿瘤治疗领域不断取得进步。随着对EBV抗原及免疫检查点抑制剂的研究,免疫治疗在R/M-NPC治疗中取得了较大进展,免疫治疗联合放化疗将成为初治高危鼻咽癌临床研究的重点。     

The Emerging Molecular Landscape of Urothelial Carcinoma

Although there have been many recent discoveries in the molecular alterations associated with urothelial carcinoma, current understanding of this disease lags behind many other malignancies. Historically, a two-pathway model had been applied to distinguish low- and high-grade urothelial carcinoma, although significant overlap and increasing complexity of molecular alterations has been recently described. In many cases, mutations in HRAS and FGFR3 that affect the MAPK and PI3K pathways seem to be associated with noninvasive low-grade papillary tumors, whereas mutations in TP53 and RB that affect the G1-S transition of the cell cycle are associated with high-grade in situ and invasive carcinoma. However, recent large-scale analyses have identified overlap in these pathways relative to morphology, and in addition, many other variants in a wide variety of oncogenes and tumor-suppressor genes have been identified. New technologies including next-generation sequencing have enabled more detailed analysis of urothelial carcinoma, and several groups have proposed molecular classification systems based on these data, although consensus is elusive. This article reviews the current understanding of alterations affecting oncogenes and tumor-suppressor genes associated with urothelial carcinoma, and their application in the context of morphology and classification schema.     

Endocrine side-effects of new anticancer therapies: Overall monitoring and conclusions

The present final consensus statement of the French Society of Endocrinology lays out the assessments that are to be systematically performed before and during anticancer treatment by immunotherapy, tyrosine kinase inhibitors or mTOR inhibitors, even without onset of any endocrinopathy. It also discusses the CTCAE adverse event grading system in oncology and the difficulty of implementing it for endocrine side-effects of these anticancer treatments. Notably, this is why certain treatment steps applied in other side-effects (e.g., high-dose corticosteroids, contraindications to immunotherapy, etc.) need to be discussed before implementation for endocrine side-effects.     

Peripheral T-cell lymphoma – are we making progress?

Peripheral T cell lymphoma (PTCL) is a rare subtype of non-Hodgkin lymphoma. PTCLs are heterogeneous in terms of biology, but generally have more aggressive features and poorer outcomes than aggressive B-cell lymphomas when treated with combination chemotherapy. While the best long-term results are still seen with intensive chemotherapeutic approaches, significant progress has been made with molecular profiling identifying genetic drivers of PTCL that could serve as therapeutic targets. Tailoring therapy to different subtypes of PTCL may lead to more individualized approaches with the hope of improved outcomes. In this paper, we review current therapies for treatment of PTCL, newly identified molecular markers, and the role of emerging therapy and novel combinations of existing agents.