Current Cancer Therapy Reviews - Volume 16, Issue 1, 2020

Breast cancer is among the foremost common malignancies and the second leading cause for cancer-related deaths in females. Varied treatment approaches are projected to cause a subject matter reduction in the fatality rate. Carcinoma treatment is highly challenging due to therapeutic resistance and reoccurrence. Several studies have revealed that bioactive compounds isolated from natural products such as plants, vegetables, and marine origins have a therapeutic and preventive role in breast carcinoma. Utilization of these bioactive agents in amelioration of cancer as complementary and alternative therapy increases day by day due to growing scientific shreds of evidence of the biomedical innovation and clinical trials. Due to the safe nature of these photochemical investigators are focusing on the investigation of lead compounds from traditional herbal medicine to discover new lead anticancer agents in the single pure compound. This review highlights the mechanism of action and future prospects of novel medicinal agents from botanical sources that have chemoprevention activity against breast carcinoma together with other types of body cancer. The major bioactive, which are used as a remedy for the prevention and treatment of breast cancer, is summarized and explored here.

The identification of new factors that may function as cancer markers and become eventual pharmacologic targets is a challenge that may influence the management of tumor development and management. Recent discoveries connecting Hsp90-binding immunophilins with the regulation of signalling events that can modulate cancer progression transform this family of proteins in potential unconventional factors that may impact on the screening and diagnosis of malignant diseases. Immunophilins are molecular chaperones that group a family of intracellular receptors for immunosuppressive compounds. A subfamily of the immunophilin family is characterized by showing structural tetratricopeptide repeats, protein domains that are able to interact with the C-terminal end of the molecular chaperone Hsp90, and via the proper Hsp90-immunophilin complex, the biological properties of a number of client-proteins involved in cancer biology are modulated. Recent discoveries have demonstrated that two of the most studied members of this Hsp90- binding subfamily of immunophilins, FKBP51 and FKBP52, participate in several cellular processes such as apoptosis, carcinogenesis progression, and chemoresistance. While the expression levels of some members of the immunophilin family are affected in both cancer cell lines and human cancer tissues compared to normal samples, novel regulatory mechanisms have emerged during the last few years for several client-factors of immunophilins that are major players in cancer development and progression, among them steroid receptors, the transctiption factor NF-ΚB and the catalytic subunit of telomerase, hTERT. In this review, recent findings related to the biological properties of both iconic Hsp90-binding immunophilins, FKBP51 and FKBP52, are reviewed within the context of their interactions with those chaperoned client-factors. The potential roles of both immunophilins as potential cancer biomarkers and non-conventional pharmacologic targets for cancer treatment are discussed.

Since the discovery of the RNA interference (RNAi) in 2006, several attempts have been made to use it for designing and developing drug treatments for a variety of diseases, including cancer. In this mini-review, we focus on the potential of small interfering RNAs (siRNA) in anticancer treatment. We first describe the significant barriers that exist on the path to clinical application of siRNA drugs. Then the current delivery approaches of siRNAs using lipids, polymers, and, in particular, polymeric carriers that overcome the aforementioned obstacles have been reviewed. Also, few siRNA mediated drugs currently in clinical trials for cancer therapy, and a collated list of siRNA databases having a qualitative and/ or quantitative summary of the data in each database have been briefly mentioned. This mini review aims to facilitate our understanding about the siRNA, their delivery systems and the possible barriers in their in vivo usage for biomedical applications.

Background: Till today cancer is still challenging to treat and needs more active therapeutic approaches. Participation of complex multi-pathway cell propagation instrument is a noteworthy issue in creating active anticancer therapeutic methodologies. Immune evasions, metabolic modifications, imperfect apoptotic component, modification in upstream or downstream RAS signaling, altered nuclear factor kappa B actions, imbalanced autophagy design and distortedly controlled angiogenesis are distinguishing features of cancer. Methods: On the basis of systemic research and analysis of the current online available database, we analyzed and reported about the key signaling pathway engaged with cancer development outlining the effectiveness of different therapeutic measures and targets that have been created or are being researched to obstruct the cancer development. Results: A number of signaling pathways, for example, resistant, metabolism, apoptosis, RAS protein, nuclear factor kappa B, autophagy, and angiogenesis have been perceived as targets for drug treatment to control the advancement, development and administration of cancer. Conclusion: A noteworthy challenge for future medication advancement is to detail a synthesis treatment influencing distinctive targets to enhance the treatment of cancer.

Introduction: Cervical cancer is the most prevalent cancer in the world due to unusual extension of cervical cell. Cervical cancer occurs due to exposure of HPV (Human papillomavirus). According to WHO, it is the 4th most ordinary cancer in women. In 2018, approx 6.6% of population was affected around the world and 570,000 new cases were reported. In low and middle-income countries, 90% of cervical cancer deaths occur. Methods: Despite various factors that cause cervical cancer are included exposure to HPV, dysregulation of CASPASE enzyme, elevated expression of IAPs (Inhibitor apoptotic protein), E6 and E7 gene of HPV, inhibition of p53, BAK, p16 upregulation, CDK-inactivation causing cervical cancer, role of VEGF, role of estrogen and its receptor in cervical cancer. Results: Cervical cancer can be screened by Pep test. There are various therapies that can be used to treat cervical cancer. As these therapies have various side effects, so the world is moving to herbal formulations to treat cervical cancer. Conclusion: In this study, we will discuss cervical cancer, its cause, symptoms, pathophysiology and treatments. Early screening and detection can help in reducing the overall burden of cervical cancer in the near future.

Background: Cancer immunotherapy is a type of cancer treatment which effectively harnesses the natural ability of the immune system to fight against cancer cells. This approach takes into consideration the fact that cancer cells express various types of antigens on their surface. Such tumor antigens can be detected by the immune system. However, cancer cells normally develop resistance to the defensive mechanisms presented by the immune system. Thus, cancer immunotherapy has some challenges in its path but due to its impressive clinical effectiveness, it is considered as the potential and effective mode of treatment for cancer. Methods: We searched the scientific database using cancer, immunotherapy, and tumor antigens as the keywords. Herein, only peer-reviewed research articles were collected which were useful to our current work. Results: Cells responsible for incurring natural immunity to the body are engineered in such a way that they become able to efficiently recognize and bind to tumor antigens. Such type of immunotherapy is referred to as active immunotherapy. Another type is passive immunotherapy, which involves the process of modifying the existing natural immune responses against cancer cells. A hybrid type of immunotherapy has also been developed which involves the combinative use of both active and passive immunotherapy. Cancer immunotherapy has so far proven to be an effective treatment for cancer as this therapy primarily aims at attacking cancer cells and not the healthy body cells lying in close vicinity to them. Conclusion: In the review, we described the significance of immunotherapy in the management of various types of cancer.

Background: Dual-targeting/Multi-targeting of oncoproteins by a single drug molecule represents an efficient, logical and alternative approach to drug combinations. In silico methods are useful tool for the search and design of selective multi-target agents. Objective: The objective of the present study was to design new hybrid compounds by linking the main structural unit of the NSAIDs with the benzothiazole and thiadiazole ring and to discover new hybrid NSAIDs as multi targeted anticancer agents through in silico approach. Method: Structure-based virtual screening was performed by applying ADMET filtration and Glide docking using Virtual screening Workflow. The docking studies were performed on three different types of receptors TNF-α, COX-II and protein kinase. Bioactivity prediction of screened compounds were done using Molinspiration online software tool. Results: Out of the 54 designed compounds eighteen were screened on the basis of binding affinity on various receptors and ADMET filtration. Bioactivity prediction reveals that screened compounds may act through kinase inhibition or enzyme inhibition. Compounds 2sa, 5sa, 6sa and 7sa showed higher binding affinity with all three receptors. Conclusion: The study concluded that compound 2sa, 5sa, 6sa, and 7sa could be further explored for multiple targeted cancer therapy.

Objective: There is a growing body of evidence that combining ipilimumab with higher doses of radiotherapy may improve the response rates and survival in patients with metastatic melanoma compared to lower doses of radiotherapy. However, the dose cutoff at which improved outcomes are more likely to occur has not been properly identified. Methods: We conducted a retrospective analysis of 100 patients treated with ipilimumab and radiotherapy for metastatic melanoma at a single institution from May 2011 to January 2017. Demographic, clinical, and treatment factors, including the biological equivalent dose (BED) with an α/β of 7, were recorded. Endpoints of interest included infield and global complete response (CR) after the completion of radiation and ipilimumab based on the RECIST criteria (v1.1) and 12-month overall survival (OS). Results: The BED cutoffs at which improved outcomes are more likely to occur are 46.5 Gy for infield CR, 50.9 Gy for global CR, and 46.5 Gy for 12 month OS. The least aggressive fractionation schedules used in this patient population that have a BED above the threshold for all 3 outcomes include 40 Gy in 20 fractions, 30 Gy in 6 fractions, and 24 Gy in 3 fractions. Conclusion: This hypothesis-generating study suggests that patients who cannot receive ablative intent radiotherapy may be more likely to benefit from concurrent radiotherapy with ipilimumab if their fractionation schedule has a BED above 46.5 - 50.9 Gy. Prospective trials evaluating this question should be considered.