Current Cancer Therapy Reviews - Volume 17, Issue 2, 2021

Glioblastoma (GBM) is a fatal type of brain cancer or primary glial neoplasm, mostly targeting aged populations. The average survival is only 15 months from the date of occurrence. It is often observed that, the invasive nature of the tumour is the main reason for poor prognosis and strong recurrence of GBM in patients even after prescribed treatments. Despite all types of therapies, it is necessary to understand the various molecular mechanisms and signalling pathways to identify targets for GBM treatment. This compilation is specifically designed to discuss Wnt signalling and Hedgehog-GLI1 pathways, which have positive and negative regulation against GBM. The recent research finding associated with different signalling pathways for GBM has also been discussed within this article.

Recently, Hasona et al. Aimed to investigate the influence of thermal radiation and magnetic field on the peristaltic flow of Carreau nanofluid in a vertical asymmetric channel. The authors have considered the Joule heating, viscous dissipation, chemical reaction, Brownian motion, thermophoresis, Soret, and Dufour effects in their study. Several mistakes and typos were discovered in the study mentioned above, which would affect the obtained results. This report outlines some of these mistakes with suggested corrections to attract the readers' attention through a more in-depth insight into analyzing and exposing these defects.

Lung cancer is a disease with higher death rates and is responsible for around 2 million deaths per year worldwide. Recently, several breakthroughs have been made in the field of lung cancer that has led to a revolution in the management of lung cancer patients. Identification of molecular markers and the implication of respective targeted therapies has been a great success in the treatment of lung adenocarcinoma patients. Despite the fact that targeted therapy of lung adenocarcinomas represents one of the significant milestones in the treatment of lung cancer that resulted in increased survival rates even in advanced stages, the mortality rates of lung cancer still remain to be significantly high. This warrants further research for gaining better insights into molecular alterations that can lead to newer innovations in targeted drug therapy towards lung adenocarcinoma. In this review, we briefly summarized the literature on molecular markers that are already in use. We also consolidated newer molecular markers that are under study with the potential for being targeted for therapies in future.

Ewing’s sarcoma (ES), also known as mesenchymal primitive neuroectodermal tumor (PNET), is a malignant round blue cell tumor (MRBCT) with a varying degree of neuronal differentiation. PNET arises from the primitive nerve cells of the central nervous system (CNS) but may also occur in the bones of the extremities, pelvis, vertebral column, and chest wall. Extraskeletal ES/PNET may affect the various soft tissues, including those of the pelvis, paraspinal region, and thoracopulmonary region. Histopathological differentiation between ES, PNET, and other related sarcomas is often difficult. On light microscopy, the same histopathological appearance of ES has been termed PNET, Askin- Rosay (A-R) tumor, and malignant neuroepithelioma by various other authors. The immunohistochemical distinction is also difficult due to poor tissue differentiation and low intake of the various specific immunohistochemical markers. The most frequent translocation is t (11; 22) (q24; q12), resulting in the EWSR1-FLI1 fusion gene detected in nearly 90% of cases and is considered the hallmark of the diagnosis of ES, PNET, atypical ES, and A-R tumor. Therefore, ES, atypical ES, PNET, and A-R tumor are currently regarded as one entity grouped together under the Ewing Family Tumor (EFT) and are treated in an identical way. EFT represents only about 3% of all pediatric malignancies. The annual incidence is between 2 and 5 cases per million children per year. The peak prevalence of the tumor is between the ages of 10 and 15 years. The incidence is higher in males than in females, with a ratio of 1.3:1. Newer groups of MRBCT that have great similarities to EFT are being recently described. These tumors, atypical EFT and Ewing’s like Sarcomas (ELS), bear similarities to EFT but have basic morphological and molecular differences. Optimal treatment requires the use of adjuvant and new-adjuvant chemotherapy (CTR), radical surgical resection and/or involves field radiotherapy (RT). The reported disease-free survival (DFS) and overall survival (OS) range between 45-80% and 36-71%, respectively. The overall prognosis for the metastatic and recurrent disease remains poor. The use of newer conventional and targeted medications, improved RT delivery, and surgical techniques may further improve the outcomes. The past few years have seen advances in genomics-based sarcoma diagnosis and targeted therapies. In this comprehensive review article, we provide a detailed report of EFT and discuss the various clinical aspects and the recent advances used in the diagnosis and treatment.

Background: Osteosarcoma is the most common type of primary bone tumor in children and adolescents, which is associated with rapid progression and poor prognosis. Multimodal therapy is the most common approach utilized for osteosarcoma management, such as the application of chemotherapy in combination with surgery or radiation therapy. Cisplatin is one of the predominantly used chemotherapeutic agents for osteosarcoma. Optimally, it is employed in combination with other chemotherapeutic drugs along with surgery or radiation therapy. Despite the availability of numerous treatment approaches, the patient survival rate has not definitively improved over the past three decades. Methods: We have summarized all findings regarding the combination of cisplatin with other chemotherapeutic agents as well as with phytochemical compounds. Results: A combination of cisplatin with a phytochemical compound synergistically enhances the killing effect of cisplatin on osteosarcoma cells with fewer side effects compared to combination with other chemotherapeutic agents. Conclusion: Conclusively, a combination of cisplatin with selected chemotherapeutic drugs has been shown to be effective. However, the unchanged survival rate has posed an urge to search for a new combination regimen. As a collaborative effort to substantiate the therapeutic efficacy, the combination with phytochemical compounds shows a promising response both in vitro as well as in the preclinical study.

The discovery of the immune checkpoint inhibitors such as programed cell death-1 protein/ Programmed death ligand-1 or 2 and (PD-1/PD-L1 or PD-L2) and Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) paved the way for developing novel cancer treatment. The check point inhibitors are found to be very efficient in treating many hot tumors (with immune environment) such as bladder cancer, melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), etc. Numerous clinical trials have been initiated to evaluate the safety and effectiveness of immune checkpoint inhibitors for patients with different cancer types, including hepatocellular carcinoma (HCC), pancreatic and prostate cancer. The results and findings of these trials are highly appreciated. However, the search for check point inhibitors with better efficacy for the treatment of HCC is still going on. The present review focuses on advancement in HCC treatments with respect to various standard therapies and immunotherapy.

Background: A cross-linking agent commonly used for cancer chemotherapy is a platinum compound such as cisplatin. However, with the acquisition of cellular drug resistance and adverse side effects, the potency of cisplatin is, therefore, often tempered. To overcome these issues, the present study has established the use of cathepsin k (CTSK) inhibitor as a potent chemosensitizer. Methods: The cytotoxic effect of cisplatin and odanacatib (ODN) on two different breast cancer patient- derived cell lines, MDA-MB-231 and MCF-7, was assessed by MTT-based colorimetric assay. The drug interaction coefficient CDI was used to evaluate the synergistically inhibitory impact of the drug combination and immunoblot was used to examine the expression of certain proteins responsible for cell survival and the mechanism of apoptosis. Results: In this study, we found that IC50 of ODN in combination with cisplatin (half of IC25) induced a synergistic cytotoxic effect in different breast cancer cells. Diminished expression of Bcl-2 and increased expression of Bax aroused the cytochrome release, that triggered caspase-9 and -3 activation in the combinatorial group. ODN with a lower dose of cisplatin significantly inhibited the protein expression of novel chemoresistant factors such as STAT3, NFΚB and IL-6. Conclusion: This study highlights the potential effects of the combination of ODN with a reduced dose of cisplatin on improving the growth inhibition and apoptosis-inducing effect on breast cancer cells via combined inhibition of NF-ΚB-induced IL-6 and STAT3 activation. The study result suggests that the further development of this novel inhibitor in combination with a low dose of standard cisplatin-based chemotherapy may contribute to an alternative treatment option for certain cancers.