Current Cancer Therapy Reviews - Volume 17, Issue 4, 2021

Introduction: Pancreatic cancer is an aggressive tumor, and an estimated 57,600 new cases and 47,050 deaths were reported in 2020 in the US alone. Recent studies have targeted the tumor microenvironment (TME) for better delivery of systemic chemotherapy, like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles were identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR= 0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), but a statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group was observed. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there was an increased incidence of serious adverse events using PEGPH20 compared to standard therapies.

Background: With the rapid evolution in advanced computer systems and various statistical algorithms, it is now a days possible to analyze complex biological data. Bioinformatics is an interface between computational and biological assemblies. It is applied in various fields of biological as well as medical sciences. Aim: The manuscript aims to summarize the developments in the field of breast cancer research through the applications of bioinformatics. Methods: Various search engines like google, science direct, Scopus, PubMed, etc., were used for the literature survey. Results: It describes the bioinformatics analysis tools and models, which include mainly artificial neural network models. Conclusion: Bioinformatics is the evolutionary approach that is used for the capturing of data from the various case studies related to breast cancer.

One of the most fatal forms of cancer includes cancer of the pancreas And the most rapid malignancy is observed in PDAC (pancreatic ductal adenocarcinoma). The high lethality rate is generally due to very late diagnosis and resistance to traditional chemotherapeutic agents. Desmoplastic stromal barrier results in resistance to immunotherapy. Other reasons for the high lethality rate include the absence of effective treatment and standard screening tests. Hence, there is a need for effective novel carrier systems. “A formulation, method, or device that allows the desired therapeutic substance to reach its site of action in such a manner that nontarget cells experience minimum effect is referred to as a drug delivery system”. The delivery system is responsible for introducing the active component into the body. They are also liable for boosting the efficacy and desirable targeted action on the tumorous tissues. Several studies, researches, and developments have yielded various advanced drug delivery systems, which include liposomes, nanoparticles, carbon nanotubules, renovoCath, etc. These systems control rate and location of the release. They are designed while taking into consideration characteristic properties of the tumor and tumor stroma. These delivery systems overcome the barriers in drug deliverance in pancreatic cancer. Alongside providing palliative benefits, these delivery systems also aim to correct the underlying reason for the defect. The following review article aims and focuses to bring out a brief idea about systems, methods, and technologies for futuristic drug deliverance in pancreatic cancer therapy.

Melanoma is an aggressive type of skin cancer, which is responsible for more deaths than nonmelanoma skin cancers. Therapeutic strategies include targeted therapy, biochemotherapy, immunotherapy, photodynamic therapy, chemotherapy, and surgical resection. Depending on the clinical stage, single or combination therapy may be used to prevent and treat cancer. Due to resistance development during treatment courses, the efficacy of mentioned therapies can be reduced. In addition to resistance, these treatments have serious side effects for melanoma patients. According to available reports, melatonin, a pineal indolamine with a wide spectrum of biological potentials, has anticancer features. Furthermore, melatonin could protect against chemotherapy- and radiation- induced adverse events and can sensitize cancer cells to therapy. The present review discusses the therapeutic application of melatonin in the treatment of melanoma. This review was carried out in PubMed, Web of Science, and Scopus databases comprising the date of publication period from January 1976 to March 2021.

Background: Colon cancer is the third leading cause of cancer-related deaths worldwide. Colon tumorigenesis is a sequential process called “Adenoma-carcinoma sequence”. The alimentary habits, obesity, heavy alcohol consumption, inflammatory bowel diseases, family history of colon cancer, oxidative stress, and cellular senescence are the major risk factor influencing colon cancer development. Senescence contributes to the aging process as well as the development and progression of colon cancer. However, the precise mechanism underlying the aging-related progress of colon cancer is yet to be answered. Recent studies proposed that the senescent cell secretes Senescence-Associated Secretory Phenotype (SASP) includes pro-inflammatory cytokines, interleukins, growth factors, and proteases actively involved in the creation of pro-tumorigenic microenvironment. Objective: This review aims to provide an overview of ROS influence cellular senescence and colon cancer development as well as summarize the antioxidant and antiaging activity of natural flavonoids. Many of the studies had reported that pro-aging genes suppress cancer and various ‘markers’ are used to identify senescent cells in vitro and in vivo. The SASP of the cells may act as a link between senescence and cancer. Conclusion: This review facilitates a better understanding and might contribute to diagnostic and prognostic systems as well as to find out the novel and targeted therapeutic approaches. Additionally, we focused on the potential role of natural flavonoids in colon cancer therapies and highlighting the flavonoid-based treatments as innovative immunomodulatory strategies to inhibit the growth of colon cancer.

In the present review, an attempt has been made to summarize the development of various Tankyrase inhibitors focussing on Wnt/beta-Catenin pathways along with other cancer targets. The last decade witnessed a plethora of research related to the role of various genetic and epigenetic events that are responsible for the progression of multistage cancers. As a result, the discovery of various signalling pathways responsible for the development of different types of cancers has resulted in the development of molecularly targeted anticancer agents. Out of the many signalling pathways, the Wnt/beta-Catenin pathways have attracted the attention of many research groups owing to their involvement in cell proliferation, role in apoptosis induction, cellular differentiation and also cell migration. The abnormal activation of this pathways has been documented in a variety of tumour cells. Another crucial factor that makes this pathway attractive to the researches is its direct involvement with poly ADP ribose polymerases. Tankyrases are poly ADP (Adenosine Diphosphate) ribose polymerases that have the capacity to inhibit Wnt/beta-Catenin pathways and become an attractive target for anticancer drugs.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality. There is a need for a marker associated with HCC progression. A disintegrin and metalloprotease (ADAMs) family proteins have a lot of functions in cell adhesion, migration, proteolysis and signaling. Aims: The aim of the study was to investigate the relation between ADAM 10 gene single nucleotide polymorphisms (SNPs) and HCC progression. Methods: This study involved 201 cases divided: Group I (67 HCC patients), Group II (67 cirrhotic patients), Group III (67 control). Each group was subjected to laboratory investigations: (CBC, blood sugar, kidney and liver function, viral markers, alpha fetoprotein), imaging: (abdominal ultrasonography, and triphasic C.T) and ADAM 10 gene polymorphism (rs 653765, rs 383902) detection by real – time PCR. Results: There was a statistically significant difference in the frequency and genotyping of ADAM10 SNPs in HCC patients in comparison to cirrhotic and control groups [the frequency of rs 653765 genotypes (p=0.015) and model (p=0.013)]; likewise, the frequency of rs 383902 genotypes (p<0.001) and model (p=0.001)). Also, there was a statistically significant association between different SNP rs 383902 genotype with CLIP stages (p=0.02) and with VISUM stages (p=0.035). Conclusion: ADAM-10 is overexpressed in HCC patients and involved in HCC progress. These findings highlight that ADAM inhibitor may be used as therapeutic goals in the treatment of HCC.

Background: GLI proteins play a significant role in the transduction of the Hedgehog (Hh) signaling pathway. A variety of human cancers, including the brain, gastrointestinal, lung, breast, and prostate cancers, demonstrate inappropriate activation of this pathway. GLI helps in proliferation and has an inhibitory role in the differentiation of hematopoietic stem cells. Malignancies may have a defect in differentiation. Different types of malignancies and undifferentiated cells have a low level of HLA expression on their cell surface. Objective: Human Leukocytic Antigen (HLA) downregulation is frequently observed in cancer cells. This work is aimed to hypothesize whether this downregulation of HLA molecules is GLI oncoprotein mediated or not. To understand the roles of different types of GLI oncoproteins on different classes of HLA transcriptional machinery was carried out through structure-based modeling and molecular docking studies. Methods: To investigate the role of GLI in HLA expression /downregulation is Hh-GLI mediated or not, molecular docking based computational interaction studies were performed between different GLI proteins (GLI1, GLI2, and GLI3) with TATA box binding protein (TBP) and compare the binding efficiencies of different HLA gene (both HLA class I and –II) regulating transcription factors (RelA, RFX5, RFXAP, RFXANK, CIITA, CREB1, and their combinations) with TBP. Due to unavailability of 3D protein structures of GLI2 and cyclin D2 (a natural ligand of GLI1) were modelled followed by structural validation by Ramachandran plot analysis. Results: GLI proteins especially, GLI1 and GLI2, have almost similar binding energy of RFX5-RFXANK- RFXAP and CIITA multi-protein complex to TBP but has lower binding energy between RelA to TBP. Conclusion: This study suggests that HLA class I may not be downregulated by GLI; however, over-expression of GLI1 is may be responsible for HLA class II downregulation. Thus this protein may be responsible for the maintenance of the undifferentiated state of malignant cells. This study also suggests the implicative role of GLI1 in the early definitive stage of hematopoiesis.

A typographical error appeared in equation in the manuscript entitled “Discussion on the paper Combined Effects of Thermal Radiation and Magnetohydrodynamic on Peristaltic Flow of Nanofluids: Applications to Radiotherapy and Thermotherapy of Cancer” by Mostafa A. Elogail in “Current Cancer Therapy Reviews”, 2021; 17(2), 93-6. We regret the error and apologize to the readers. The original article can be found online at https://www.eurekaselect.com/189490/article