Current Pharmaceutical Design - Volume 27, Issue 45, 2021

Background: Glioblastoma is a grade IV astrocytoma with an average survival span for patients of 18 months after initial diagnosis and no standard treatment protocol is available. Therefore, there is a need to search for novel approaches to target glioblastoma. Objectives: This review intends to capture the role of immunoglobulin-M in cancer, more specifically in glioblastoma multiforme (GBM), and to compile the latest developments and immunological pathways relevant to glioblastoma. Methods: Information on glioblastoma, cancer microenvironment, cancer therapeutics, and how to improve the scenario were obtained from scientific literature databases such as Pubmed, Medline, Google Scholar, Science Direct, Springer, Wiley online library, and some data was harvested from regulatory and compliance databases such as clinicaltrials.gov, FDA database, and WHO Globocan. Results and Conclusion: Currently, only a limited number of therapies are approved for GBM, and no standard care is in place in case of disease relapse, necessitating a possible broader perspective in looking at the disease and its underlying mechanisms.

Cancer is a global concern leading to millions of deaths every year. A declining trend in new drug discovery and development is becoming one of the major issues among the pharmaceutical, biotechnology industries and regulatory agencies. New drug development is proven to be a very lengthy and a costly process. Launch of a new drug takes 8-12 years and huge investments. Success rate in oncology therapeutics is also low due to toxicities at the pre-clinical and clinical trials level. Many oncological drugs get rejected at very promising stage showing adverse reactions on healthy cells. Thus, exploring new therapeutic benefits of the existing, shelved drugs for their anti-cancerous action could result in a therapeutic approach preventing the toxicities which occurs during clinical trials. Drug repurposing has the potential to overcome the challenges faced via conventional way of drug discovery and is becoming an area of interest for researchers and scientists. Although very few in vivo studies are conducted to prove the anti-cancerous activity of the drugs. Insufficient in vivo animal studies and lack of human clinical trials are the lacuna in the field of drug repurposing. This review focuses on the aspect of drug repurposing for cancer therapeutics. There are various studies which show that drugs approved for clinical indications other than cancer have shown promising anti-cancer activities. Some of the commonly used drugs like Benzodiazepines (Diazepam, Midzolam), Antidepressants (Imipramine, Clomipramine, and Citalopram), Antiepileptic (Valporic acid, Phenytoin), Anti diabetics (metformin) etc., have been reported to show potential activity against the cancerous cells.

Background: Glioblastoma multiforme is the most malignant form of high-grade astrocytoma. Clinically it is characterized as 4^th grade of astrocytoma having necrotic tissue and hyperplastic blood vessel. It is observed to be the most frequent adult brain tumor representing an overall 15.4% of all brain tumors and about 60-75% of the entire astrocytoma. There are limited therapies available, and the most widely used therapy includes surgical intrusion followed by radiotherapy plus chemotherapy (paclitaxel, temozolomide, docetaxel, etc.), with an overall patient survival rate from 6-14 months. Various studies have proved that nanoformulations offer considerable advantages like enhanced drug solubility, targeted activity, and attenuated side effects. Objective: The key objective of this review article is to exemplify numerous studies carried out using nanocarriers for overcoming the challenges associated with the treatment of glioblastoma. It also describes the pathways associated with the induction, initiation, and progression of glioblastoma. Methods: Research articles that focused on the use of nanocarrier-based drug delivery approach for the treatment of various glioblastoma were collected from different search engines such as Google Scholar, Science Direct, and PubMed using keywords like glioblastoma, nanocarriers, brain delivery, etc. Results: Nanocarriers have shown enormous potential in overcoming the challenges associated with the treatment of glioblastoma. Conclusion: Broad research is essential so that these nanocarriers can be used clinically for the welfare of mankind, in the management of glioblastoma, in the near future.

Background: Cancer is a wide range cellular level disease that occurs when cells go through uncontrolled division and growth. The mechanisms by which the cells undergo metastasis are complex and involve many interactions between the tumor cells and their cellular environment. Matrix metalloproteinases (MMPs) have been found to over-express at various stages of tumor progression and their inhibition using MMP inhibitors has been a subject of potential therapy against cancer. Objective: This review discusses recent research in MMP inhibitors (MMPI) used for preventing tumor progression. Methods: In this review, we explored the role of MMPs in cancer progression and summarized the current developments in MMPIs, their role in cancer suppression in in vitro and in vivo studies and their evaluation in clinical trials from the current research data. Results: MMPIs have shown to be very successful in in vitro models, cell lines and in some in vivo studies. Unfortunately, their efficacy in clinical trials has been found to be hit and miss. Recent studies have shown that the novel delivery approaches of MMP inhibitors may enhance their therapeutic effects towards the prevention of cancer. Conclusion: In this review, we presented different MMP inhibitors, their performance at different stages of models - in vitro, in vivo, small animal models and eventually clinical trials. We provide newer methods of MMPI delivery that may be better targeted to suppress only specific MMPs and avoid toxic side effects in healthy cells.

Breast cancer is one of the leading types among the common non-cutaneous malignancies in women. All the curative methods available for its treatment are minimal due to their toxicity issues and dose-related side effects. Various evolving nanotechnology techniques displayed the opportunity to target breast cancer. One such delivery system is lipid-based drug delivery systems (LDDS). This concept is constrained only for the laboratory scale should be shifted to the industrial level targeting the nanomedicine with clinical benefits. This work tried to portray the advancements in the LDDS along with the lipid-based excipients, advantages, disadvantages and applications. It even helped in highlighting the recently developed lipid-based nanocarriers for breast cancer management.

The field of oncology is vast and ever-growing. The present cancer therapeutics is continually exhibiting various drawbacks, which opens the door for exploring better novel therapeutic techniques. One such emerging technique is the manipulation of gut microbiota to induce a positive curative effect in the body. The dynamic gut microbiota of our body houses an astonishing number of microorganisms, mainly bacteria. The balance of the gut microbiota is essential for good health as imbalances may result in dysbiosis leading to various diseases such as cancer. The gut microbiota can be manipulated by using prebiotics, probiotics, synbiotics, postbiotics, and antibiotics for better therapeutic outcomes, as well as to improve the quality of life of patients undergoing conventional cancer treatment. Administration of bacteria as a probiotic agent accompanied with prebiotics obtained from a wide variety of herbs has been used effectively to enhance the treatment of various cancers. Although the theoretical basis of Gut therapy can be ascertained, further clinical trials will be essential to determine the scope and limitations fully. The present review provides a glimpse of conventional and novel cancer therapeutics and their drawbacks, along with the role of the gut microbiome and its modulation to design new pharmaceutics against cancer.

Mutations and their manifestations in the form of various diseases and disorders result in cancer which is a major cause of human death worldwide. A considerable amount of information is available at the cellular, molecular and genetic levels regarding the occurrence and spread of precarious cancer; yet, there is no cure. The traditional methods of treatment such as chemotherapy, radiotherapy and surgical intervention have shown to be moderately effective and to keep some types of cancer under control, but each modality has its own advantages and disadvantages. In recent years, more advanced methods such as targeted therapies, immunotherapy, and precision medicine are shown to be promising, and these fields continue to expand rapidly along with the conventional methods. This review focuses on the reports of advanced methods of treatment from a scientific standpoint to recognize many new and modern approaches. Selective targeting of the tumour cells by nanoparticle-based novel drug delivery approaches includes the latest innovations in their preparation strategies and applications. The concept of precision medicine and its impact on treatment are highlighted here with the hope of individualised therapy with minimum side effects as a part of ever-expanding treatment strategies. Additional challenges related to cancer treatment like multi-drug resistance and toxicity are also deliberated in brief. Based on the available reports and scientific evidence, better targeted approaches with better quality clinical outcomes and more precise drug delivery to fit individual treatment needs are anticipated in the near future to control this deadly disease.

Background: Breast cancer is the most prevalent cancer amongst females across the globe, and with over 2 million new cases reported in 2018, it poses a huge economic burden to the already dwindling public health. A dearth of therapies in the pipeline to treat triple-negative breast cancers and acquisition of resistance against the existing line of treatments urge the need to strategize novel therapeutics in order to add new drugs to the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks breast cancer progression. Objective: While four HDACi have been approved by the FDA for the treatment of different cancer types, no HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered. Conclusion: This review attempts to set the stage for the rational structure-based discovery of isoform-selective HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes and individual landscape. The development of inhibitors in accordance with the differential expression of HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective inhibitors, adopting a ‘personalized-medicine’ approach.

Objective: Available conventional therapies are commonly used for the treatment of breast cancer, such as surgical procedures, hormonal therapy, radiation therapy, and chemotherapy. These therapies can be either given alone or in combination with other therapies. Various side effects associated with chemotherapies, including toxicity and multidrug resistance, have limited the use of chemotherapy, thus making it less effective than the above mentioned therapies. This review focus has been summarised as the application of anticancer with phytoconstituents that could be a promising and effective treatment strategy for breast cancer treatment. Methods: This review is designed on relevant literature that was screened on the basis of in-scope criteria in the title, abstract, and keywords of the searched articles. The available literature was searched on PubMed, ScienceDirect, MedlinePlus, and Google scholar up to May 2021. A total of 47 articles were selected out of 168 articles based on inclusion and exclusion criteria. Results: The major limitations accompanying available conventional treatment, mainly chemotherapy, include low bioavailability at the specific site of tumor cells, the occurrence of multidrug resistance, and high doserelated side effects. The phytoconstituents possessing anticancer properties and, when used in combination with chemotherapeutic agents, impart promising and potential therapeutic value. Many in vitro and in vivo studies showed that phytoconstituents could enhance the effectiveness of chemotherapy drugs for breast cancer treatment. Conclusion: The combination approaches of phytoconstituents with chemotherapeutic drugs provide less toxicity to normal cells, reduce side effects, and overcome multidrug resistance, thus making the combination approaches an effective strategy for the treatment of breast cancer.