Cancers

Review

17 pages, 314 KiB

Open AccessFeature PaperReview

Novel Targeted Agents in Advanced and Recurrent Low-Grade Serous Ovarian Cancer: A Silver Lining in the Therapy of a Chemoresistant Disease?

by Arina Onoprienko, Thomas Bartl, Christoph Grimm, Nicole Concin and Stephan Polterauer

Cancers 2024, 16(19), 3268; https://doi.org/10.3390/cancers16193268 - 26 Sep 2024

Cited by 2 | Viewed by 1894

Abstract

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment [...] Read more.

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

18 pages, 282 KiB

Open AccessReview

Palliative Thoracic Radiotherapy in the Era of Modern Cancer Care for NSCLC

by Lucyna Kępka

Cancers 2024, 16(17), 3018; https://doi.org/10.3390/cancers16173018 - 29 Aug 2024

Viewed by 1185

Abstract

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher [...] Read more.

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher radiation doses administered over longer periods have shown modest survival benefits. These findings stem from studies conducted before the advent of immunotherapy and targeted therapy in clinical practice. Currently, there are no large prospective studies specifically dedicated to palliative radiotherapy conducted in this new treatment era. Modern radiotherapy technologies are now widely available and are increasingly used for palliative purposes in selected patients, reflecting the expanded array of therapeutic options for disseminated NSCLC and improved prognosis. Some traditional tenets of palliative thoracic radiotherapy, such as the improvement of overall survival with a protracted radiation schedule and the use of simple, cost-effective radiation techniques for palliative purposes, may no longer hold true for patients receiving immunotherapy or targeted therapy. The application of IMRT or SBRT in the context of palliative radiotherapy for NSCLC is not yet sufficiently explored, and this is addressed in this review. Moreover, new risks associated with combining palliative radiotherapy with these systemic treatments are being explored and are discussed within the context of palliative care. The optimal timing, doses, fractionation schedules, and treatment volumes for radiotherapy combined with immunotherapy or targeted therapy are currently subjects of investigation. In emergencies, radiotherapy should be used as a life-saving measure without delay. However, for other indications of palliative thoracic radiotherapy, decisions regarding doses, timing relative to systemic treatments, and treatment volumes should be made in a multidisciplinary context, considering the patient’s prognosis, anticipated outcomes, and access to potentially effective treatments. We still lack robust data from prospective studies on this matter. This review examines and discusses available evidence on the use of palliative thoracic radiotherapy within the framework of modern treatment strategies for NSCLC. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

40 pages, 1433 KiB

Open AccessReview

Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?

by Ahmed M. Elshazly, Jingwen Xu, Nebras Melhem, Alsayed Abdulnaby, Aya A. Elzahed, Tareq Saleh and David A. Gewirtz

Cancers 2024, 16(17), 2989; https://doi.org/10.3390/cancers16172989 - 28 Aug 2024

Cited by 2 | Viewed by 1601

Abstract

Tyrosine kinase inhibitors (TKIs) represent a relatively large class of small-molecule inhibitors that compete with ATP for the catalytic binding site of tyrosine kinase proteins. While TKIs have demonstrated effectiveness in the treatment of multiple malignancies, including chronic myelogenous leukemia, gastrointestinal tumors, non-small [...] Read more.

Tyrosine kinase inhibitors (TKIs) represent a relatively large class of small-molecule inhibitors that compete with ATP for the catalytic binding site of tyrosine kinase proteins. While TKIs have demonstrated effectiveness in the treatment of multiple malignancies, including chronic myelogenous leukemia, gastrointestinal tumors, non-small cell lung cancers, and HER2-overexpressing breast cancers, as is almost always the case with anti-neoplastic agents, the development of resistance often imposes a limit on drug efficacy. One common survival response utilized by tumor cells to ensure their survival in response to different stressors, including anti-neoplastic drugs, is that of autophagy. The autophagic machinery in response to TKIs in multiple tumor models has largely been shown to be cytoprotective in nature, although there are a number of cases where autophagy has demonstrated a cytotoxic function. In this review, we provide an overview of the literature examining the role that autophagy plays in response to TKIs in different preclinical tumor model systems in an effort to determine whether autophagy suppression or modulation could be an effective adjuvant strategy to increase efficiency and/or overcome resistance to TKIs. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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26 pages, 2616 KiB

Open AccessReview

The Anticancer Activity of Monosaccharides: Perspectives and Outlooks

by Niamh McCallum and Mohammad Najlah

Cancers 2024, 16(16), 2775; https://doi.org/10.3390/cancers16162775 - 6 Aug 2024

Cited by 2 | Viewed by 2104

Abstract

A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake [...] Read more.

A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake and consumption of glucose. The Warburg effect may be exploited in the treatment of cancer; certain epimers and derivatives of glucose can enter cancer cells and inhibit glycolytic enzymes, stunting metabolism and causing cell death. These include common dietary monosaccharides (ᴅ-mannose, ᴅ-galactose, ᴅ-glucosamine, ʟ-fucose), as well as some rare monosaccharides (xylitol, ᴅ-allose, ʟ-sorbose, ʟ-rhamnose). This article reviews the literature on these sugars in in vitro and in vivo models of cancer, discussing their mechanisms of cytotoxicity. In addition to this, the anticancer potential of some synthetically modified monosaccharides, such as 2-deoxy-ᴅ-glucose and its acetylated and halogenated derivatives, is reviewed. Further, this article reviews how certain monosaccharides can be used in combination with anticancer drugs to potentiate conventional chemotherapies and to help overcome chemoresistance. Finally, the limitations of administering two separate agents, a sugar and a chemotherapeutic drug, are discussed. The potential of the glycoconjugation of classical or repurposed chemotherapy drugs as a solution to these limitations is reviewed. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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20 pages, 722 KiB

Open AccessReview

Breast Cancer Stem Cells and Tumor Heterogeneity: Characteristics and Therapeutic Strategies

by Aleksandra Romaniuk-Drapała, Ewa Totoń, Magdalena Taube, Malgorzata Idzik, Błażej Rubiś and Natalia Lisiak

Cancers 2024, 16(13), 2481; https://doi.org/10.3390/cancers16132481 - 7 Jul 2024

Cited by 2 | Viewed by 4227

Abstract

Breast cancer is one of the most frequently detected malignancies worldwide. It is responsible for more than 15% of all death cases caused by cancer in women. Breast cancer is a heterogeneous disease representing various histological types, molecular characteristics, and clinical profiles. However, [...] Read more.

Breast cancer is one of the most frequently detected malignancies worldwide. It is responsible for more than 15% of all death cases caused by cancer in women. Breast cancer is a heterogeneous disease representing various histological types, molecular characteristics, and clinical profiles. However, all breast cancers are organized in a hierarchy of heterogeneous cell populations, with a small proportion of cancer stem cells (breast cancer stem cells (BCSCs)) playing a putative role in cancer progression, and they are responsible for therapeutic failure. In different molecular subtypes of breast cancer, they present different characteristics, with specific marker profiles, prognoses, and treatments. Recent efforts have focused on tackling the Wnt, Notch, Hedgehog, PI3K/Akt/mTOR, and HER2 signaling pathways. Developing diagnostics and therapeutic strategies enables more efficient elimination of the tumor mass together with the stem cell population. Thus, the knowledge about appropriate therapeutic methods targeting both “normal” breast cancer cells and breast cancer stem cell subpopulations is crucial for success in cancer elimination. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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16 pages, 286 KiB

Open AccessReview

Current and Future of Robotic Surgery in Thyroid Cancer Treatment

by Joonseon Park and Kwangsoon Kim

Cancers 2024, 16(13), 2470; https://doi.org/10.3390/cancers16132470 - 6 Jul 2024

Cited by 2 | Viewed by 2946

Abstract

Thyroid cancer is among the most common endocrine malignancies, necessitating effective surgical interventions. Traditional open cervicotomy has long been the standard approach for thyroidectomy. However, the advent of robotic surgery has introduced new possibilities for minimally invasive procedures with benefits in terms of [...] Read more.

Thyroid cancer is among the most common endocrine malignancies, necessitating effective surgical interventions. Traditional open cervicotomy has long been the standard approach for thyroidectomy. However, the advent of robotic surgery has introduced new possibilities for minimally invasive procedures with benefits in terms of cosmetic outcomes, enhanced precision, comparable complication rates, and reduced recovery time. This study mainly reviewed the most widely used and well-known robotic thyroidectomy approaches: the transaxillary approach, the bilateral axillo–breast approach, and the transoral approach. This review examines the current status and future potential of robotic surgery in thyroid cancer treatment, comparing its efficacy, safety, and outcomes with those of conventional open cervicotomy. Challenges such as a longer operative time and higher costs exist. Future directions include technological advancements, tele-surgery, single-port surgery, and the integration of artificial intelligence. Robotic surgery holds promise in optimizing patient outcomes in thyroid cancer treatment. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

24 pages, 1369 KiB

Open AccessReview

Promising Combinatorial Therapeutic Strategies against Non-Small Cell Lung Cancer

by Prabhjot Kaur, Santosh Kumar Singh, Manoj K. Mishra, Shailesh Singh and Rajesh Singh

Cancers 2024, 16(12), 2205; https://doi.org/10.3390/cancers16122205 - 12 Jun 2024

Cited by 5 | Viewed by 2390

Abstract

Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals’ cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research [...] Read more.

Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals’ cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research and therapies is continually shaping the landscape of NSCLC diagnosis and management. The treatment of NSCLC has undergone significant advancements in recent years, especially with the emergence of targeted therapies that have shown remarkable efficacy in patients with actionable mutations. This has ushered in the era of personalized medicine in NSCLC treatment, with improvements in molecular and immunohistochemical techniques contributing to enhanced progression-free survival. This review focuses on the latest progress, challenges, and future directions in developing targeted therapies for NSCLC, including tyrosine kinase inhibitors (TKIs), DNA-damaging agents, immunotherapy regimens, natural drug therapy, and nanobodies. Furthermore, recent randomized studies have demonstrated enhanced overall survival in patients receiving different targeted and natural drug therapies. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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18 pages, 3733 KiB

Open AccessReview

Historical Perspective and Current Trends in Anticancer Drug Development

by Katarzyna Gach-Janczak, Joanna Drogosz-Stachowicz, Anna Janecka, Karol Wtorek and Marek Mirowski

Cancers 2024, 16(10), 1878; https://doi.org/10.3390/cancers16101878 - 15 May 2024

Cited by 5 | Viewed by 4133

Abstract

Cancer is considered one of the leading causes of death in the 21st century. The intensive search for new anticancer drugs has been actively pursued by chemists and pharmacologists for decades, focusing either on the isolation of compounds with cytotoxic properties from plants [...] Read more.

Cancer is considered one of the leading causes of death in the 21st century. The intensive search for new anticancer drugs has been actively pursued by chemists and pharmacologists for decades, focusing either on the isolation of compounds with cytotoxic properties from plants or on screening thousands of synthetic molecules. Compounds that could potentially become candidates for new anticancer drugs must have the ability to inhibit proliferation and/or induce apoptosis in cancer cells without causing too much damage to normal cells. Some anticancer compounds were discovered by accident, others as a result of long-term research. In this review, we have presented a brief history of the development of the most important groups of anticancer drugs, pointing to the fact that they all have many side effects. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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23 pages, 2949 KiB

Open AccessReview

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy

by Marianna Ciwun, Anna Tankiewicz-Kwedlo and Dariusz Pawlak

Cancers 2024, 16(6), 1240; https://doi.org/10.3390/cancers16061240 - 21 Mar 2024

Cited by 3 | Viewed by 10154

Abstract

Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of [...] Read more.

Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of cancer cells. The mechanism of action of LDN depends on the dose and duration of the OGFr blockade, leading to a compensatory increase in the synthesis of the opioid growth factor (OGF), which has an inhibitory effect on carcinogenesis. Numerous studies on in vitro and in vivo models provide evidence of LDN’s positive impact on inhibiting the OGF–OGFr axis in cancers. LDN’s unique mechanism of action on cancer cells, lack of direct cytotoxic effect, and immunomodulating action form the basis for its use as an adjuvant in chemotherapy and immunotherapy of cancerous lesions. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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24 pages, 1648 KiB

Open AccessReview

Targeting STAT3 and NF-κB Signaling Pathways in Cancer Prevention and Treatment: The Role of Chalcones

by Violetta Krajka-Kuźniak, Marta Belka and Katarzyna Papierska

Cancers 2024, 16(6), 1092; https://doi.org/10.3390/cancers16061092 - 8 Mar 2024

Cited by 12 | Viewed by 2412

Abstract

Chalcones are a type of natural flavonoid compound that have been found to possess promising anticancer properties. Studies have shown that chalcones can inhibit the growth and proliferation of cancer cells, induce apoptosis, and suppress tumor angiogenesis. In addition to their potential therapeutic [...] Read more.

Chalcones are a type of natural flavonoid compound that have been found to possess promising anticancer properties. Studies have shown that chalcones can inhibit the growth and proliferation of cancer cells, induce apoptosis, and suppress tumor angiogenesis. In addition to their potential therapeutic applications, chalcones have also been studied for their chemopreventive effects, which involve reducing the risk of cancer development in healthy individuals. Overall, the anticancer properties of chalcones make them a promising area of research for developing new cancer treatments and preventative strategies. This review aims to provide a thorough overview of the central studies reported in the literature concerning cancer prevention and the treatment of chalcones. Although chalcones target many different mechanisms, the STAT and NF-κB signaling pathways are the ones this review will focus on, highlighting the existing crosstalk between these two pathways and considering the potential therapeutic opportunities for chalcone combinations. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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30 pages, 2609 KiB

Open AccessEditor’s ChoiceReview

Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy

by Ryungsa Kim, Takanori Kin and William T. Beck

Cancers 2024, 16(5), 984; https://doi.org/10.3390/cancers16050984 - 28 Feb 2024

Cited by 21 | Viewed by 6330

Abstract

Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the c-Jun/activator protein 1 (AP-1)/p53 [...] Read more.

Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the c-Jun/activator protein 1 (AP-1)/p53 signaling pathway leading to apoptotic death is altered. Cancer cells treated with anticancer drugs undergo c-Jun/AP-1–mediated apoptotic death and are involved in c-Jun N-terminal kinase activation and growth arrest- and DNA damage-inducible gene 153 (Gadd153)/CCAAT/enhancer-binding protein homologous protein pathway induction, regardless of the p53 genotype. Gadd153 induction is associated with mitochondrial membrane permeabilization after anticancer drug treatment and involves a coupled endoplasmic reticulum stress response. The induction of apoptosis by anticancer drugs is mediated by the intrinsic pathway (cytochrome c, Cyt c) and subsequent activation of the caspase cascade via proapoptotic genes (e.g., Bax and Bcl-xS) and their interactions. Anticancer drug-induced apoptosis involves caspase-dependent and caspase-independent pathways and occurs via intrinsic and extrinsic pathways. The targeting of antiapoptotic genes such as Bcl-2 enhances anticancer drug efficacy. The modulation of apoptotic signaling by Bcl-xS transduction increases the sensitivity of multidrug resistance-related protein-overexpressing epidermoid carcinoma cells to anticancer drugs. The significance of autophagy in cancer therapy remains to be elucidated. In this review, we summarize current knowledge of cancer cell death-related signaling pathways and their alterations during anticancer drug treatment and discuss potential strategies to enhance treatment efficacy. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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18 pages, 3641 KiB

Open AccessReview

Targeted Therapeutic Strategies for the Treatment of Cancer

by Benjamin Victoir, Cécile Croix, Fabrice Gouilleux and Gildas Prié

Cancers 2024, 16(2), 461; https://doi.org/10.3390/cancers16020461 - 22 Jan 2024

Cited by 21 | Viewed by 4866

Abstract

Extensive research is underway to develop new therapeutic strategies to counteract therapy resistance in cancers. This review presents various strategies to achieve this objective. First, we discuss different vectorization platforms capable of releasing drugs in cancer cells. Second, we delve into multitarget therapies [...] Read more.

Extensive research is underway to develop new therapeutic strategies to counteract therapy resistance in cancers. This review presents various strategies to achieve this objective. First, we discuss different vectorization platforms capable of releasing drugs in cancer cells. Second, we delve into multitarget therapies using drug combinations and dual anticancer agents. This section will describe examples of multitarget therapies that have been used to treat solid tumors. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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20 pages, 1432 KiB

Open AccessReview

The Role of Macrophages in Sarcoma Tumor Microenvironment and Treatment

by Agnieszka E. Zając, Anna M. Czarnecka and Piotr Rutkowski

Cancers 2023, 15(21), 5294; https://doi.org/10.3390/cancers15215294 - 5 Nov 2023

Cited by 10 | Viewed by 10286

Abstract

Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas [...] Read more.

Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas by expressing specific markers and secreting factors that influence immune and tumor cells. They are involved in many signaling pathways, such as p-STAT3/p-Erk1/2, PI3K/Akt, JAK/MAPK, and JAK/STAT3. TAMs also significantly impact the clinical outcomes of patients suffering from sarcomas and are mainly related to poor overall survival rates among bone and soft tissue sarcomas, for example, chondrosarcoma, osteosarcoma, liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma. This review summarizes the current knowledge on TAMs in sarcomas, focusing on specific markers on sarcoma cells, cell–cell interactions, and the possibly involved molecular pathways. Furthermore, we discuss the clinical significance of macrophages in sarcomas as a potential target for new therapies, presenting clinical relevance, possible new treatment options, and ongoing clinical trials using TAMs in sarcoma treatment. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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13 pages, 699 KiB

Open AccessReview

Making the Case for Autophagy Inhibition as a Therapeutic Strategy in Combination with Androgen-Targeted Therapies in Prostate Cancer

by Ahmed M. Elshazly and David A. Gewirtz

Cancers 2023, 15(20), 5029; https://doi.org/10.3390/cancers15205029 - 18 Oct 2023

Cited by 6 | Viewed by 2088

Abstract

Androgen receptor targeting remains the primary therapeutic strategy in prostate cancer, encompassing androgen biosynthesis inhibitors and androgen receptor antagonists. While both androgen-receptor-positive and “castration-resistant” prostate cancer are responsive to these approaches, the development of resistance is an almost inevitable outcome leading to the [...] Read more.

Androgen receptor targeting remains the primary therapeutic strategy in prostate cancer, encompassing androgen biosynthesis inhibitors and androgen receptor antagonists. While both androgen-receptor-positive and “castration-resistant” prostate cancer are responsive to these approaches, the development of resistance is an almost inevitable outcome leading to the castration-resistant form of the disease. Given that “cytoprotective” autophagy is considered to be a predominant mechanism of resistance to various chemotherapeutic agents as well as to radiation in the cancer literature, the purpose of this review is to evaluate whether autophagy plays a central role in limiting the utility of androgen deprivation therapies in prostate cancer. Unlike most of our previous reports, where multiple functional forms of autophagy were identified, making it difficult if not impossible to propose autophagy inhibition as a therapeutic strategy, the cytoprotective form of autophagy appears to predominate in the case of androgen deprivation therapies. This opens a potential pathway for improving the outcomes for prostate cancer patients once effective and reliable pharmacological autophagy inhibitors have been developed. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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20 pages, 2081 KiB

Open AccessReview

Unraveling the Anticancer Potential of Statins: Mechanisms and Clinical Significance

by Mohamed Y. Zaky, Chuanwen Fan, Huan Zhang and Xiao-Feng Sun

Cancers 2023, 15(19), 4787; https://doi.org/10.3390/cancers15194787 - 29 Sep 2023

Cited by 21 | Viewed by 2963

Abstract

Statins are an essential medication class in the treatment of lipid diseases because they inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They reduce cholesterol levels and reduce the risk of cardiovascular disease in both primary and secondary prevention. In addition to their powerful pharmacologic suppression [...] Read more.

Statins are an essential medication class in the treatment of lipid diseases because they inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They reduce cholesterol levels and reduce the risk of cardiovascular disease in both primary and secondary prevention. In addition to their powerful pharmacologic suppression of cholesterol production, statins appear to have pleitropic effects in a wide variety of other diseases by modulating signaling pathways. In recent years, statins have seen a large increase in interest due to their putative anticancer effects. Statins appear to cause upregulation or inhibition in key pathways involved in cancer such as inhibition of proliferation, angiogenesis, and metastasis as well as reducing cancer stemness. Further, statins have been found to induce oxidative stress, cell cycle arrest, autophagy, and apoptosis of cancer cells. Interestingly, clinical studies have shown that statin use is associated with a decreased risk of cancer formation, lower cancer grade at diagnosis, reduction in the risk of local reoccurrence, and increasing survival in patients. Therefore, our objective in the present review is to summarize the findings of the publications on the underlying mechanisms of statins’ anticancer effects and their clinical implications. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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24 pages, 2304 KiB

Open AccessReview

Advantages of the Combinatorial Molecular Targeted Therapy of Head and Neck Cancer—A Step before Anakoinosis-Based Personalized Treatment

by Robert Kleszcz

Cancers 2023, 15(17), 4247; https://doi.org/10.3390/cancers15174247 - 24 Aug 2023

Cited by 5 | Viewed by 2142

Abstract

The molecular initiators of Head and Heck Squamous Cell Carcinoma (HNSCC) are complex. Human Papillomavirus (HPV) infection is linked to an increasing number of HNSCC cases, but HPV-positive tumors generally have a good prognosis. External factors that promote the development of HPV-negative HNSCC [...] Read more.

The molecular initiators of Head and Heck Squamous Cell Carcinoma (HNSCC) are complex. Human Papillomavirus (HPV) infection is linked to an increasing number of HNSCC cases, but HPV-positive tumors generally have a good prognosis. External factors that promote the development of HPV-negative HNSCC include tobacco use, excessive alcohol consumption, and proinflammatory poor oral hygiene. On a molecular level, several events, including the well-known overexpression of epidermal growth factor receptors (EGFR) and related downstream signaling pathways, contribute to the development of HNSCC. Conventional chemotherapy is insufficient for many patients. Thus, molecular-based therapy for HNSCC offers patients a better chance at a cure. The first molecular target for therapy of HNSCC was EGFR, inhibited by monoclonal antibody cetuximab, but its use in monotherapy is insufficient and induces resistance. This article describes attempts at combinatorial molecular targeted therapy of HNSCC based on several molecular targets and exemplary drugs/drug candidates. The new concept of anakoinosis-based therapy, which means treatment that targets the intercellular and intracellular communication of cancer cells, is thought to be the way to improve the clinical outcome for HNSCC patients. The identification of a link between molecular targeted therapy and anakoinosis raises the potential for further progress in HPV-negative HNSCC therapy. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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