Current Cancer Therapy Reviews - Volume 20, Issue 6, 2024

Childhood cardiac tumors are rare but challenging conditions that can have a significant impact on a child's health and even be fatal if not detected and diagnosed timely. While various types of tumors can occur in the heart, the most common among children are benign tumors, such as rhabdomyomas. Diagnosis of pediatric cardiac tumors is often challenging and requires a combination of clinical examination, imaging studies and biopsy. In some cases, the tumors may be asymptomatic and discovered incidentally, while in others, they can cause symptoms, such as shortness of breath, chest pain, arrhythmias and congestive heart failure. Treatment options for pediatric cardiac tumors vary depending on the type, size and location of the tumor and may include surgical resection, watchful waiting or a combination of both. The prognosis for children with cardiac tumors is generally good, with a high rate of complete cure in many cases. However, long-term follow-up and monitoring are important to detect and manage any potential complications or recurrence of the tumors.

Skin cancer is a prevalent and diverse group of malignancies affecting the skin, with three primary types: basal cell carcinoma, squamous cell carcinoma, and melanoma. Each subtype varies in terms of its histological origin, behavior, and potential for metastasis. Despite advances in treatment, skin cancer poses challenges due to biological barriers that hinder drug delivery, multidrug resistance mechanisms that limit treatment effectiveness, and the complex interplay of genetic alterations driving tumorigenesis. Current treatment strategies encompass a spectrum of approaches, including chemotherapies, immunotherapies, gene therapies, and innovative techniques such as photothermal therapy, iontophoretic therapy, electroporation therapy, microneedle array therapy, and nanotechnology- based treatments. The latter involves liposomes, niosomes, carbon nanotubes, dendrimers, hydrogels, and gold nanoparticles, all tailored to enhance drug delivery and therapeutic efficacy. Additionally, herbal drug-based therapy harnesses the potential of natural compounds to target various aspects of skin cancer progression. This review provides an overview of skin cancer types, challenges in treatment, and an extensive exploration of current therapeutic strategies, highlighting the everevolving landscape of innovative approaches that promise to transform how skin cancer is managed.

Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

In recent years, the use of natural compounds derived from plants for the treatment of skin cancer has gained significant attention due to their potential therapeutic effects and minimal side effects. This review focuses on the innovative approach of utilizing biocomponents sourced from plants in combination with backpropagation neural networks (BPNN) for the screening and analysis of skin cancer treatments. The integration of plant-derived compounds and AI-driven algorithms holds promise for enhancing the precision and effectiveness of skin cancer therapies. The review begins by highlighting the escalating global burden of skin cancer and the limitations of conventional treatment approaches. With the rise in concerns about the adverse effects of synthetic drugs, researchers have turned their attention towards exploring the therapeutic potential of plant-derived biocomponents. These natural compounds are known for their rich bioactive constituents that exhibit anti-cancer properties, making them suitable candidates for skin cancer treatment. One of the key challenges in harnessing the potential of plant-derived compounds is the need for accurate screening and analysis of their effects. This is where backpropagation neural networks, a type of artificial neural network, comes into play. These networks can process complex data and recognize intricate patterns, enabling them to predict the efficacy of various biocomponents in combating skin cancer. The review delves into the functioning of BPNN and its applications in drug discovery and treatment evaluation. Furthermore, the review explores several case studies that demonstrate the successful integration of plant-derived compounds with BPNN in the context of skin cancer treatment. These studies provide evidence of how this synergistic approach can lead to improved treatment outcomes by minimizing adverse effects and maximizing therapeutic benefits. The methodology section discusses the steps involved in training the neural network using relevant datasets and optimizing its performance for accurate predictions. While the integration of plant-derived compounds and BPNN shows great promise, the review also addresses the existing challenges and limitations. These include the need for comprehensive and standardized datasets, potential biases in training data, and the complexity of neural network architectures. The regulatory considerations surrounding plant-based therapies are also discussed, highlighting the importance of rigorous testing and validation.

Vitamin D and Vitamin D Receptors have gained more importance beyond their roles in bone metabolism and calcium homeostasis. Several epidemiological studies have confirmed that vitamin D has a specific function in a wide variety of gynecological cancers, such as ovarian cancer, endometrial cancer, cervical cancer, uterine fibroid, and vulvar cancer. The different anti-cancer mechanisms exerted by vitamin D on tumor cells are cell proliferation, cancer progression, angiogenesis, cell cycle arrest, and inflammation. The role of vitamin D is well emphasized in ovarian cancer and uterine fibroids, with limited studies available on cervical cancer and other types of gynecological cancers. Overall, most epidemiological data support that inadequate or low levels of vitamin D in the circulation are associated with risk and poor prognosis in several types of gynecological cancer. It is evident that vitamin D plays a prominent role as an anticancer agent against numerous types of cancer. This review focuses on the etiology and role of vitamin D and the Vitamin D Receptor in various types of gynecological cancer, as well as the mechanism of Vitamin D and its metabolites in the management of gynecological cancer.

Introduction: Bibliometric analysis quantitatively examines scientific literature to extract insights. This article has conducted such analysis on glioblastoma multiforme (GBM) treatment articles. GBM, a prevalent brain tumor, is typically treated with surgery, radiation, and chemotherapy. Objectives: The article aimed to bibliometrically analyze articles discussing combined GBM treatment to identify impactful research areas and encourage collaboration. Materials and Methods: The study encompassed a comprehensive search in the Scopus database, spanning articles published from 1974 to 2022. Inclusion criteria encompassed research conducted in the Americas, both clinical and experimental. A total of 772 articles were collected and categorized based on their primary focus on combined treatment approaches. Results: Clinical studies constituted 52% of articles, suggesting a slight dominance. The analysis unveiled key research moments, including a 1998 focus shift and a pivotal 2005 study on temozolomide- radiation combination. Top journals, trends, and authors were identified, with the USA leading in contributions. Discussions: Despite high brain tumor incidence, research distribution discrepancy is concerning. Regional epidemiological studies have been endorsed. The dominance of US and German authors in GBM collaboration has raised equity issues due to budget and GDP disparities limiting Latin American representation. Conclusion: GBM research in the region is dominated by the USA, while contributions from Latin American countries remain limited. The absence of comprehensive epidemiological studies on GBM in Latin America is concerning, considering the evident impact of the disease in the region. This underscores the urgent need for increased research participation and collaboration to advance the understanding and treatment of GBM across Latin American nations.

Objective: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) comprise a new subgroup of thyroid tumors of follicular origin with borderline histologic features that lack evidence of either capsular or vascular invasion. In contrast to the invasive follicular variant of papillary thyroid carcinoma (IFVPTC), adverse events such as cancer-related death, distant or regional metastases, and structural or biochemical recurrence do not occur in patients with NIFTP. Many studies have been done to elucidate these two specific types of papillary thyroid cancer (PTC) and reduce aggressive therapeutic actions. This study compares molecular, cytological, and radiologic features of NIFTP and IFVPTC. Materials and Methods: Two groups of patients with NIFTP and IFVPTC (n = 18 in each group) who were referred to the endocrine clinic, at Imam Reza Hospital, were enrolled in this crosssectional study. Molecular analysis for BRAFV600E mutation of thyroid tissue was evaluated for all cases. Patient data included: age, sex, type of surgery, thyroid sonographic findings, and prior cytological diagnosis with the Bethesda system for reporting thyroid cytopathology. Results: Only two cases in the IFVPTC group were positive for BRAFV600E mutation. The majority of NIFTP cases were diagnosed as benign lesions (8/18). In contrast, the majority of IFVPTC cases were diagnosed as suspicious for malignancy on cytology (7/18). The mean nodule size in ultrasound in the NIFTP group (41.81 ± 20.43 mm) was larger than the IFVPTC group (36.72 ± 20.73 mm) (p =0.47). Most cases in the IFVPTC group had significantly multiple nodules (72.2%), while most cases in the NIFTP group (81.3%) had solitary nodules. Nodule composition in both groups was solid and complex; however, no cystic nodules were detected in ultrasound examinations. Furthermore, no calcification or lymphadenopathy was seen in the majority of cases in ultrasound. In the IFVPTC group, 47.1% and 35.3% of nodules were hyperechoic and hypoechoic, respectively, while 23.1%, 38.5%, and 23.1% of nodules in the NIFTP group were heterogenic, hyperechoic, and hypoechoic, respectively. Conclusion: According to our findings, only 11.1% of IFVPTC cases were BRAFV600E-positive, while none of the patients in the NIFTP group showed this mutation. However, IFVPTC was predominantly associated with a preceding diagnosis of PTC on FNA, and NIFTP was associated with the preceding diagnosis of benign lesions and follicular neoplasm. Sonographic findings failed to distinguish NIFTP from IFVPTC.

Background: Academic clinical research is considered the most important for cancer research because it frequently tests novel drug combinations, investigates rarer diseases, and lowers the risk for future commercial investments. However, due to the potential risks to the cancer patient, clinical research is governed by strict regulations. In high-income countries, comprehensive cancer centers (CCCs) have been established to align academic clinical cancer research with the regulatory framework. In comparison, academic clinical cancer research is considered ineffective in low-income countries. Methods: A cross-sectional, online survey was conducted to evaluate the knowledge of Indian health science students regarding cutting-edge cancer therapeutics and their underlying regulatory requirements. Results: The survey found that 163 out of the 265 respondents were aware of the challenges of developing safe and effective anticancer therapeutics. 43 respondents found no challenges, while 59 respondents were unaware of any. Out of 163, 44 respondents identified technical challenges, 31 identified regulatory issues, and 88 identified both challenges in developing novel anticancer therapeutics. Interestingly, only 83 students out of 265, study cancer therapy regulations in their curriculum. This clearly indicates that most of India's health science students have a significant lack of understanding about the regulations for new cancer treatments. Conclusion: Academic clinical cancer research in India is just recognized as a prerequisite for degree completion due to a lack of regulatory foundation. An emphasis should be placed on restructuring the coursework offered to health science students to improve their ability to translate theoretical cancer research to real-world clinical care.

Purpose: Oncological medications face a myriad of challenges, including technological, pre-clinical, clinical, and manufacturing, that lead to regulatory approval delays or failures. The present study aims to identify some challenges encountered by researchers or regulators during the development of novel cancer therapies. Methods: The present cross-sectional observational study used a mixed-method design methodology. The participants were selected via a non-random sampling method via self-selection and snowballing approach. A survey questionnaire was developed and circulated among the selected participants as a hard copy or email or a Google form. Open-ended and closed-ended questions were incorporated to identify the regulatory challenges faced during oncology drug development. The responses were collected from September 2021 to June 2022. These responses were then coded and themes were identified for the challenges. Results: A total of 87 responses were obtained for the questionnaire among the individuals contacted. Seven themes were identified from the collated responses that depicted the challenges for the regulatory approval of anticancer drug products. The majority of responders (38.2%) suggested reduced approval time whereas endpoint selection and study design were considered as a challenge by 12.0% of responders each. Furthermore, 6.0% of responders admit that timely interaction with the regulators is also a challenge that delays approval. Many challenges also exist during the product development phase; hence, 12.0% of responders reported safety issues, and 22.0% of responders reported technical issues during manufacturing as the cause of regulatory failure. Moreover, 12.0% of responders suggested the need for improvements in regulatory guidelines for oncology drug development. Conclusion: The survey indicates a lack of Indian guidelines for anticancer products, whereas limited guidance is available from other countries such as Europe or the United States. Thus, the survey points to the necessity for improvement in the regulatory guidelines and drug approval process to address the challenges unique to cancer drug development.