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Palliative systemic therapy for recurrent or metastatic nasopharyngeal carcinoma - How far have we achieved?

Lee V, Kwong D, Leung TW, Lam KO, Tong CC, Lee A

Crit Rev Oncol Hematol, 2017 Jun;114:13-23.
PMID: 28477740 DOI: 10.1016/j.critrevonc.2017.03.030

Nasopharyngeal carcinoma (NPC) is endemic in Southern China, Taiwan, Malaysia, Singapore, North Africa and Alaska. About 30% of NPC patients develop recurrence or metastasis despite initial radical treatment. Palliative chemotherapy is the first-line treatment for inoperable recurrence or distant metastatic disease. However the standard first-line chemotherapeutic regimen is yet to be established until recently gemcitabine and cisplatin has been proven superior to traditional regimen with 5-FU and cisplatin shown in a phase III randomized-controlled trial. Further palliative systemic treatment options including other chemotherapeutic regimens, targeted therapy and more recently immunotherapy have gradually evolved. We provided a comprehensive review on different traditional chemotherapeutic regimens and highlighted the latest chemotherapeutic treatments as well as the latest development of targeted therapies, immune checkpoint inhibitors and other immunotherapeutic options in this setting.
E-cadherin: Its dysregulation in carcinogenesis and clinical implications

Wong SHM, Fang CM, Chuah LH, Leong CO, Ngai SC

Crit Rev Oncol Hematol, 2018 Jan;121:11-22.
PMID: 29279096 DOI: 10.1016/j.critrevonc.2017.11.010

E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics.
Culture-independent studies on bacterial dysbiosis in oral and oropharyngeal squamous cell carcinoma: A systematic review

Gopinath D, Menon RK, Banerjee M, Su Yuxiong R, Botelho MG, Johnson NW

Crit Rev Oncol Hematol, 2019 Jul;139:31-40.
PMID: 31112880 DOI: 10.1016/j.critrevonc.2019.04.018

Imbalance within the resident bacterial community (dysbiosis), rather than the presence and activity of a single organism, has been proposed to be associated with, and to influence, the development and progression of various diseases; however, the existence and significance of dysbiosis in oral/oropharyngeal cancer is yet to be clearly established. A systematic search (conducted on 25/01/2018 and updated on 25/05/2018) was performed on three databases (Pubmed, Web of Science & Scopus) to identify studies employing culture-independent methods which investigated the bacterial community in oral/oropharyngeal cancer patients compared to control subjects. Of the 1546 texts screened, only fifteen publications met the pre-determined selection criteria. Data extracted from 731 cases and 809 controls overall, could not identify consistent enrichment of any particular taxon in oral/oropharyngeal cancers, although common taxa could be identified between studies. Six studies reported the enrichment of Fusobacteria in cancer at different taxonomic levels whereas four studies reported an increase in Parvimonas. Changes in microbial diversity remained inconclusive, with four studies showing a higher diversity in controls, three studies showing a higher diversity in tumors and three additional studies showing no difference between tumors and controls. Even though most studies identified a component of dysbiosis in oral/oropharyngeal cancer, methodological and analytical variations prevented a standardized summary, which highlights the necessity for studies of superior quality and magnitude employing standardized methodology and reporting. Indeed an holistic metagenomic approach is likely to be more meaningful, as is understanding of the overall metabolome, rather than a mere enumeration of the organisms present.
Antineoplastic-related cardiovascular toxicity: A systematic review and meta-analysis in Asia

Leong SL, Chaiyakunapruk N, Lee SWH

Crit Rev Oncol Hematol, 2019 Sep;141:95-101.
PMID: 31272046 DOI: 10.1016/j.critrevonc.2019.05.017

BACKGROUND: Cancer and heart diseases are the leading causes of morbidity and mortality in many countries worldwide. Recent advancement in chemotherapy and targeted therapies has led to an improvement in cancer survival rates, but at a cost of higher cardiac side effects. However, report on antineoplastic-related cardiotoxicities incidence in Asia is lacking.
METHODS: We systematically searched multiple databases to identify studies reporting incidence of antineoplastic-related cardiovascular toxicity in Asia published from inception to November 2018. Pre-specified subgroups were performed to explore heterogeneity and study quality assessed and reported according to PRISMA guidelines.
RESULTS: A total of 61 studies across 11 countries in Asia reported 8 types of cardiovascular toxicities were included. These studies mostly reported on adult populations, and usually examined cardiotoxicities related to anthracycline use. The most frequently reported cardiotoxicities were heart failure, electrocardiogram abnormalities and left ventricular dysfunction. The pooled estimated incidence of cardiotoxicity was 4.27% (95% CI: 3.53-5.07). Subgroup analysis showed higher incidence in middle income countries compared to high income countries.
CONCLUSIONS: Although robust incidence studies are sparse, cardiovascular complications affects approximately one in twenty cancer patients in Asia. This highlights a unique opportunity of cancer patients caring that need cardiologists and oncologist to become familiar with this emerging sub-specialty.
The TRAIL to cancer therapy: Hindrances and potential solutions

Wong SHM, Kong WY, Fang CM, Loh HS, Chuah LH, Abdullah S, et al.

Crit Rev Oncol Hematol, 2019 Nov;143:81-94.
PMID: 31561055 DOI: 10.1016/j.critrevonc.2019.08.008

Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. Resistance to apoptosis is a hallmark of virtually all malignancies. Despite being a cause of pathological conditions, apoptosis could be a promising target in cancer treatment. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of TNF cytokine superfamily. It is a potent anti-cancer agent owing to its specific targeting towards cancerous cells, while sparing normal cells, to induce apoptosis. However, resistance occurs either intrinsically or after multiple treatments which may explain why cancer therapy fails. This review summarizes the apoptotic mechanisms via extrinsic and intrinsic apoptotic pathways, as well as the apoptotic resistance mechanisms. It also reviews the current clinically tested recombinant human TRAIL (rhTRAIL) and TRAIL receptor agonists (TRAs) against TRAIL-Receptors, TRAIL-R1 and TRAIL-R2, in which the outcomes of the clinical trials have not been satisfactory. Finally, this review discusses the current strategies in overcoming resistance to TRAIL-induced apoptosis in pre-clinical and clinical settings.
Clinical significance of aberrant microRNAs expression in predicting disease relapse/refractoriness to treatment in diffuse large B-cell lymphoma: A meta-analysis

Ting CY, Liew SM, Price A, Gan GG, Bee-Lan Ong D, Tan SY, et al.

Crit Rev Oncol Hematol, 2019 Dec;144:102818.
PMID: 31733445 DOI: 10.1016/j.critrevonc.2019.102818

The clinical significance of aberrantly expressed microRNAs in predicting treatment response to chemotherapy in diffuse large B-cell lymphoma patients (DLBCL) remains uncertain. Feasibility of microRNA testing to predict treatment outcome was evaluated. Twenty-two types of aberrantly expressed microRNAs were associated with poor treatment response; pooled hazard ratio (HR) was 2.14 [95%CI:1.78-2.57, P
MicroRNAs serving as potential biomarkers and therapeutic targets in nasopharyngeal carcinoma: A critical review

Lee KT, Tan JK, Lam AK, Gan SY

Crit Rev Oncol Hematol, 2016 Jul;103:1-9.
PMID: 27179594 DOI: 10.1016/j.critrevonc.2016.04.006

Despite significant medical advancement, nasopharyngeal carcinoma (NPC) remains one of the most difficult cancers to detect and treat where it continues to prevail especially among the Asian population. miRNAs could act as tumour suppressor genes or oncogenes in NPC. They play important roles in the pathogenesis of NPC by regulating specific target genes which are involved in various cellular processes and pathways. In particular, studies on miRNAs related to the Epstein Barr virus (EBV)-encoded latent membrane protein one (LMP1) and EBVmiRNA- BART miRNA confirmed the link between EBV and NPC. Both miRNA and its target genes could potentially be exploited for prognostic and therapeutic strategies. They are also important in predicting the sensitivity of NPC to radiotherapy and chemotherapy. The detection of stable circulating miRNAs in plasma of NPC patients has raised the potential of miRNAs as novel diagnostic markers. To conclude, understanding the roles of miRNA in NPC will identify ways to improve the management of patients with NPC.
IL-1α and colorectal cancer pathogenesis: Enthralling candidate for anti-cancer therapy

Cheng KJ, Mejia Mohammed EH, Khong TL, Mohd Zain S, Thavagnanam S, Ibrahim ZA

Crit Rev Oncol Hematol, 2021 Jul;163:103398.
PMID: 34147647 DOI: 10.1016/j.critrevonc.2021.103398

Inflammation has been well-established as a hallmark of colorectal cancer (CRC). Interleukin-1 alpha (IL-1α) is one of the primary inflammatory mediators driving the pathogenesis of inflammation-associated CRC. This systematic review presents the roles of IL-1α in the pathogenesis of the disease. Bibliographic databases PubMed, Science Direct, Scopus and Web of Science were systematically searched for articles that addresses the relationship between IL-1α and colorectal cancer. We highlighted various mechanisms by which IL-1α promotes the pathogenesis of CRC including enhancement of angiogenesis, metastasis, resistance to therapy, and inhibition of tumour suppressive genes. We also discussed the potential mechanisms by which IL-1α expression is induced or secreted in various studies. Beyond these, the systematic review also highlights several potential therapeutic strategies which should be further explored in the future; to target IL-1α and/or its associated pathways; paving our way in finding effective treatments for CRC patients.