Clinical Cancer Drugs - Volume 8, Issue 1, 2021

Background: Cancer is one of the significant causes of morbidity and mortality in patients globally. Lung cancer, among other cancers, remains to be one of the principal causes of deaths in both men and women. The most common type of lung cancer is non-small-cell lung cancer (NSCLC). Apart from lung cancer, pancreatic cancer is also currently one of the common cancers. Objective: The assessment of QoL in erlotinib-treated patients can also prove to be very useful in the establishment of this drug as the main treatment option for patients with pancreatic and lung cancer. Methods: Therapies that target EGFR-mediated signaling are the latest keystones for treating these two types of cancers. They comprise of two main treatment modalities: firstly, against the extracellular fields that include monoclonal antibodies, and secondly, mechanisms that create interferences in the signaling pathways, primarily the small molecule tyrosine kinase inhibitors. Results: Quality of life (QoL) is one of the key advantages of erlotinib therapy over chemotherapy. Conclusion: The present review reports the role of Erlotinib in improving the quality of life of cancer patients, especially in NSCLC and pancreatic cancers. The studies or trials establishing the relations between Erlotinib and QoL are discussed in detail in this review.

American Cancer Society estimates that about 1 in 21 men and 1 in 23 women in US will develop colorectal cancer during their lifetime. Due to the advances in screening and treatment modalities, the mortality rate has reduced. Rising resistance to treatment has directed the focus towards different approaches as combination therapies involving different treatment techniques available. One such approach is chemo-immunotherapy that aims to modulate TIME and improve the response to immunotherapy. The chemo-immunotherapy has shown a positive impact on improving the outcome of CRC treatment. The ensemble of results discussed herein supports the role of biomarkers in determining the most effective treatment algorithm. Comprehensive knowledge about the off-target effects of the cytotoxic drugs helps in designing more efficacious combined treatment. The time-window for optimal combination must also be considered carefully.

Diarylheptanoids are widely distributed among species belonging to the family Betulaceae. Being highly polar in nature, they can either be isolated from plants by using sophisticated chromatographic techniques or can be synthesized in the laboratory. They are found to exhibit a wide range of activities, from very simple analgesics to anticancer agents. Recently, they have gained considerable attention due to inhibitory activity against NF-ΚB activation, NO and TNF-α production, reduction in NO and COX-2 levels in a dose-dependent manner, and suppression of Tcell activation. The current review article highlights the role of diarylheptanoids as potent anticancer agents in a variety of cancers.

Background: Endoplasmic reticulum to nucleus signaling 1 (ERN1) is a major signaling pathway of endoplasmic reticulum stress and is crucial for malignant tumor growth. Objective: The article aims to discuss the recent progress in the discovery of endoplasmic reticulum stress targets and their involvement in tumor growth. Methods: Literature from the PubMed database related to the endoplasmic reticulum stress involvement in the tumor growth and chemoresistance was searched and reviewed. Results: The endoplasmic reticulum stress plays an important part in malignant tumor growth and is involved in invasion and metastasis. Inhibition of protein kinase and endoribonuclease activities of the ERN1 signaling protein significantly reduces tumor growth through down-regulation of angiogenesis and cell proliferation but activates the invasion. ERN1 knockdown affects the expression of many genes associated with the regulation of apoptosis, cell proliferation, and survival as well as reprograms the hypoxic regulation of most gene expressions. Simultaneously, inhibition of ERN1 endoribonuclease only has a stronger suppressive effect on tumor growth and decreases the invasiveness. Conclusion: Present review summarizes the recent advances in inhibiting ERN1 signaling that regulates tumor growth. Further understanding of the regulatory mechanisms of genome reprogramming upon inhibition of ERN1 signaling may help discover new possibilities for developing novel effective therapeutics.

Background: The ongoing COVID-19 pandemic has forced oncologists to alter their daily practice, despite the lack of substantial evidence, in order to reduce the risk of transmission among patients with underlying malignant and other concurrent medical conditions. Objective: This systematic review compares the characteristics of oncology-focused COVID-19 manuscripts published from January 1st to April 30th, 2020, and from September 1st to September 30th, 2020, to identify the variation of publications between the start of the pandemic and our current state. Methods: The PubMed database was searched on two different occasions using the search string “Cancer OR Tumor” AND “COVID-19 OR SARS-CoV-2”. All manuscripts pertaining to COVID-19 and oncological topics were included in this review. Results: The search from January 1st to April 30th, 2020 and from September 1st to September 30th, 2020, resulted in 299 and 249 articles pertaining to our objective, respectively. Comparing the earlier with later publication period, the proportion of articles containing original data increased from 22.4% to 44.2%, whereas the proportion of Editorials/Correspondences decreased from 43.5% to 20.5%. Cancer patient management guidelines accounted for the majority of publications during both periods (59.2% versus 43.4%, respectively). Conclusion: The study revealed a rapidly increasing number of COVID-19 and oncological-focused publications throughout the pandemic thus far. Given the unprecedented nature of the COVID-19 pandemic, future analyses are expected to reveal rapidly evolving publication patterns.

Background: By considering [6]-gingerol as an important polyphenol, ginger has been related to cancer. Objective: The main objective of this study is to evaluate the ginger extract on the expressions of four genes from different categories involved in breast cancer in Balb/C mice after 14 days. Methods: In terms of this research, ethanol extraction methods for extracting ginger rhizomes with the goal of increasing [6]-gingerol were used. In this regard, a MTT test was accomplished for the whole ginger extract to confirm its effect on the 4T1 breast cancer cell line (murine mammary carcinoma cell). Afterward, the transplanted breast cancer Balb/C mouse was used to be treated with the whole ginger extract (0.02 g/kg of mouse weight). The expressions of STAT3, β-catenin, P53, APC, genes were evaluated, after 14-day of treatment. Results: The results showed that 70% ethanol and microwave extraction method can be considered as the best method for extracting ginger extract. The expression of β-catenin has decreased in the blood and liver of the treated group. Moreover, the expression of STAT3 oncogenes has significantly decreased in the liver tissue. In addition, the expressions of APC suppressor genes have increased in the blood and liver. Conclusion: In conclusion, treatment by 0.02 g/kg of mouse weight of ginger extract after 14 days increased the expressions of APC as suppressor genes and a β-catenin oncogene in blood and liver of the breast cancer group.

Background: Breast cancer is the most frequently diagnosed cancer in women worldwide. Pyronaridine (PND), an antimalarial drug, was shown to exert anticancer activity on seventeen different human cancer cells, seven from female breast tissue. Additionally, PND induced apoptosis via mitochondrial depolarization, alteration of cell cycle progression, and DNA intercalation. However, the molecular target of PND in cells was not elucidated. Objective: Here, we have further investigated PND's mode of action by using transcriptome analysis. Preclinical studies were also performed to determine whether PND could affect tumor progression in a human breast cancer xenograft in mice. Moreover, we assessed the combined efficacy of PND with well-known anticancer drugs. Methods: Transcriptome analyses of PND-treated cancer cells were performed. Topoisomerase II activity was evaluated by an in vitro assay. In addition, daily oral administration of PND was given to mice with human breast cancer xenografts. The differential nuclear staining assay measured in- -vitro cell toxicity. Results: The transcriptome signatures suggested that PND might act as a topoisomerase II inhibitor. Thus, topoisomerase inhibition assays were performed, providing evidence that PND is a bona fide topoisomerase II inhibitor. Also, in-vivo studies suggest that PND hinders tumor progression. Besides, combination studies of PND with anticancer drugs cisplatin and gemcitabine revealed higher cytotoxicity against cancer cells than individual drug administration. Conclusion: The findings provide evidence that PND is a topoisomerase II inhibitor and can hinder cancer progression in an animal model, further demonstrating PND's favorable characteristics as a repurposed anticancer drug.

Background: In the last decades, growing evidence demonstrates interest in phytoestrogen intake to modulate targets in different types of cancer. Plant lignans have proven efficacious in blocking estrogen receptors of breast cancer cells. Among them, four phytoestrogen lignans: pinoresinol, matairesinol, lariciresinol, and secoisolariciresinol have been most studied. However, available studies have mostly dealt with the anti-cancer effects of groups of lignans in certain foods or plants and the effects of specific lignans, especially from a molecular interaction viewpoint, have been rarely addressed in the literature. Objective: We aimed to in silico predict pharmacological properties, binding ability and binding strength of pinoresinol, matairesinol, lariciresinol and secoisolariciresinol as possible inhibitors of estrogen receptor alpha which is the most important biomarker in breast cancer. Methods: Firstly, we evaluated the pharmacological properties of four lignans using SwissADME. Then we investigated the ligand-receptor interactions of these molecules as positively appraised ligands for ER-positive breast cancer targeted therapy using docking method. We finally compared the inhibitory effect possibility of the lignans against endoxifen which is the active metabolite of tamoxifen. Results: The best binding affinity of endoxifen, matairesinol, pinoresinol, lariciresinol and secoisolariciresinol were respectively -9.2, -7.5, -6.7, -6.7, -5.8 kcal/mol. In the meantime, matairesinol showed a minimum binding energy than other studied lignans in addition to the most similar interactions to endoxifen with conserved domain residues of the active site pocket in Leu:391, Ala:350, Met:421, and Phe:404. Conclusion: Among the studied lignans, matairesinol showed favorable pharmacokinetics and drug-likeliness properties, the least binding energy as well as the most common interactions in conserved residues of the active site pocket with estrogens. This makes it a molecule with low number of nonspecific interactions, better target selectivity, and hence fewer side effects. Thus, our results introduce matairesinol as a possibly effective anti-estrogen receptor inhibitor candidate.