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Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor progn

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… HH signaling pathway in RCC. 253 HH signaling pathway may interact with hypoxia-inducible factor 2α modulating the radiosensitivity of RCC. 254 Furukawa et al. suggested that Gli2 may be related to the underlying mechanism of drug resistance associated with tyrosine kinase inhibitor (TKI) inhibitors sunitinib …

Chemokines: humble yet mighty players in the tumour microenvironment.

Chemokines are tiny chemotactic cytokines which play a crucial role in pathophysiology by maintaining homeostasis and inflammation. Their role in the tumour microenvironment is very much puzzling because of both pro- and anti-tumourigenic effects. Chemokines have gained much attention today, since it has been recognized that they are game changers in the TME via controlling immune cell recruitment, angiogenesis, metastasis, tumour growth and drug resistance. In this review, we are exploring the role of several chemokines and their receptors in the TME with special focus on immune cell recruitm

Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.

Persistent stimulation from cancer antigens leads to T lymphocytes (T cells) exhaustion, with up-regulated expression of co-inhibitory receptors, including programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These receptors collectively impair T cell function via distinct molecular pathways, contributing to immune evasion and cancer progression. This review highlights the therapeutic promise of immune checkpoint inhibito

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, u

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… Melatonin suppresses Akt/mTOR/S6K activity, induces cell apoptosis, and synergistically inhibits cell growth with sunitinib in renal carcinoma cells via reversing Warburg effect Redox Rep. 2023 28 2251234 10.1080/13510002.2023.2251234 37642220 PMC10472857 101. Mediavilla M.D. Cos S. …

Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative review.

As new molecular tracers are identified to target specific receptors, tissue, and tumor types, opportunities arise for the development of both diagnostic tracers and their therapeutic counterparts, termed "theranostics." While diagnostic tracers utilize positron emitters or gamma-emitting radionuclides, their theranostic counterparts are typically bound to beta and alpha emitters, which can deliver specific and localized radiation to targets with minimal collateral damage to uninvolved surrounding structures. This is an exciting time in molecular imaging and therapy and a step towards personal

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… In the early stages, Octreotide and other targeted therapies like sunitinib, everolimus, capecitabine, and temozolomide have shown response in this setting [56] . It is notable that, as early as 2009, PRRT has been used as neoadjuvant therapy and successfully reported in a case report [57] . …

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of C

Cancer-associated stroke: Pathophysiology, detection and management (Review).

Numerous types of cancer have been shown to be associated with either ischemic or hemorrhagic stroke. In this review, the epidemiology and pathophysiology of stroke in cancer patients is discussed, while providing vital information on the diagnosis and management of patients with cancer and stroke. Cancer may mediate stroke pathophysiology either directly or via coagulation disorders that establish a state of hypercoagulation, as well as via infections. Cancer treatment options, such as chemotherapy, radiotherapy and surgery have all been shown to aggravate the risk of stroke as well. The clin

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… When examining patients treated with sunitinib, a multi-targeted tyrosine kinase FDA approved for the treatment of renal cell carcinoma, pancreatic neuroendocrine tumors and gastrointestinal stromal tumors, 7.6% of them presented high-grade (NCI Grade 3 or 4) thrombocytopenia ( 54 ). …

Combination therapy in combating cancer.

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival

Neuropathic cancer pain: What we are dealing with? How to manage it?

Cancer pain is a serious health problem, and imposes a great burden on the lives of patients and their families. Pain can be associated with delay in treatment, denial of treatment, or failure of treatment. If the pain is not treated properly it may impair the quality of life. Neuropathic cancer pain (NCP) is one of the most complex phenomena among cancer pain syndromes. NCP may result from direct damage to nerves due to acute diagnostic/therapeutic interventions. Chronic NCP is the result of treatment complications or malignancy itself. Although the reason for pain is different in NCP and non

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… A phase 1 Bayesian dose selection study of bortezomib and sunitinib in patients with refractory solid tumor malignancies. Br J Cancer. 2013;108(4):762–765. doi: 10.1038/bjc.2012.604. 80. Cavaletti G, Jakubowiak AJ. …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… Temsirolimus for renal cell carcinoma, and most of the drugs such as methoxyestradiol, Echinomycin, Geldanamycin, etc. , were terminated either at phase I or II for not showing significant advantages in clinical trials. 150 Anti-vascular endothelial growth factor agents, for example, Bevacizumab, Cediranib, Sunitinib …

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of cli

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… (2017) Cisplatin | QTc interval prolongation | Thix et al. (2009) Secondary | Anthracyclines | Cardiomyopathy | Buza et al. (2017) 5-Fluorouracil | Myocardial ischemia | Khan, et al. (2012) bortezomib, carfilzomib | Heart failure | Buza et al. (2017) Dasatinib | Cardiomyopathy | Buza et al. (2017) sunitinib …

Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?

Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypep

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… hepatocellular carcinoma cells at concentrations of up to 100 µM [ 7 , 67 , 68 , 122 , 143 , 150 ], and a recent study using DPP-IV + renal cell carcinoma stem cells demonstrated that sitagliptin had no effect on the growth of these cells, but enhanced their sensitivity to the tyrosine kinase inhibitor, sunitinib …

Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma.

Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to th

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… Inhibitors of tyrosine kinases such as sunitinib and sorafenib were clinically approved for the treatment of various tumor diseases. In addition, sorafenib displayed considerable activity in a phase 2 trial for pemetrexed/platinum-pretreated malignant mesothelioma [ 228 ]. …

The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acqui

Metabolic reprogramming in cancer and senescence.

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. Statistical data show that cancer incidence and mortality rates show a clear upward trend with age. Although there is a commonality between dysregulated nutrient sensing, which is one of the main features of aging, and metabolic reprogramming of tumor cells, the specific regulatory relationship is not clear. This manuscript intends to comprehensively analyze the relationship between senescence and tumor metabolic reprogramming; as well as reveal the impac

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… Adult connective tissue proliferative small round cell tumor | Phase 2 | NCT01120275 AMPK | 6‐Mercaptopurine | Malignant glioma | Phase 1 | NCT06279767 | Placebo | Hepatocellular carcinoma | Phase 1 | NCT02261844 | Metformin rapamycin | Breast tumor Lung tumor Liver cancer | Phase 1 | NCT02145559 | Sunitinib …

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer.

In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does n

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… anticancer therapy | | - Venous TE: • Cisplatin-based chemotherapy • Cytostatic: capecitabine, gemcitabine, paclitaxel • Tamoxifen • Immunomodulatory drugs: thalidomide, lenalidomide - Arterial TE: • Aromatase inhibitors • Androgen-deprivation therapy • VEGF-targeted drugs (eg, bevacizumab, ramucirumab , sunitinib …

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and

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… The subject was treated after nephrectomy with the tyrosine kinase inhibitors (sunitinib) followed by a combination of anti-PD-1 antibody (AB) pembrolizumab and stereotactic body radiation therapy (SBRT) (32 Gy, four fractions). …

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 1 : National Harbor, MD, USA. 6-10 November 2019.

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