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Heat shock protein 90 and role of its chemical inhibitors in treatment of hematologic malignancies.

Heat shock protein 90 (Hsp90) is a conserved and constitutively expressed molecular chaperone and it has been shown to stabilize oncoproteins and facilitate cancer development. Hsp90 has been considered as a therapeutic target for cancers and three classes of Hsp90 inhibitors have been developed: (1) benzoquinone ansamycin and its derivatives, (2) radicicol and its derivates, and (3) small synthetic inhibitors. The roles of these inhibitors in cancer treatment have been studied in laboratories and clinical trials, and some encouraging results have been obtained. Interestingly, targeting of Hsp

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… Immunogenic apoptosis in human acute myeloid leukemia (AML): Primary human aml cells expose calreticulin and release heat shock protein (Hsp) 70 and Hsp90 during apoptosis Oncol. Rep. 2011 25 1549 1556 21431284 10.3892/or.2011.1229 62. Yeh C.H. Tseng R. Hannah A. Estrov Z. Estey E. Kantarjian H. …

Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing.

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed d

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… Furthermore, VPA induced immunogenic cell death in BC cells by eliciting calreticulin exposure and reducing CD47 expression on the cell surface, thereby altering the ‘do not eat me’ signal [ 84 ]. …

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

Recent advances in oncolytic virotherapy: insights from clinical trials and combination treatment strategies.

Background and aimOncolytic virotherapy is a novel therapeutic paradigm in oncology that uses viruses to selectively replicate within cancer cells, causing targeted tumor cell destruction with minimal toxicity to healthy tissues. With the rapid growth of oncolytic virotherapy and the accumulation of clinical studies on this subject, the present review aims to provide a comprehensive evaluation of current achievements in cancer treatments involving oncolytic viruses (OVs).Main textNumerous clinical trials have been conducted to assess the therapeutic efficacy and safety of OVs across a variety

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… ICD is a form of cell death that elicits a strong and durable immune response through the release of damage-associated molecular patterns (DAMPs) such as ATP, calreticulin (CRT), and HMGB1 from damaged cells [ 25 ]. … By destroying tumor cells, Adenovirus (Ad5/3-hTERT-E1A-hCD40L) can release tumor antigens and generate danger signals such as calreticulin, HMGB1, and ATP, which enhance immunogenicity and trigger apoptosis, contributing to immunogenic cell death. …

Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.

Thymoquinone (TQ), the active compound in Nigella sativa (black seed), has shown promising effects against cancer in many laboratory studies. In this review, we explore how TQ works on different aspects of cancer, from stopping cancer cell growth and spread, to triggering cancer cell death, reducing inflammation, and helping the immune system fight back. We also highlight how TQ may overcome one of the biggest problems in cancer treatment-chemoresistance. When used together with common treatments like chemotherapy, radiation, or immunotherapy, TQ has been shown to improve their effects and red

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… Investigating TQ’s impact on immunogenic cell death markers, such as calreticulin exposure and ATP release, may also provide insight into its potential to enhance anti-tumor immunity. …

Cardiotoxicity of Novel Targeted Hematological Therapies.

Chemotherapy-related cardiac dysfunction, also known as cardiotoxicity, is a group of drug-related adverse events negatively affecting myocardial structure and functions in patients who received chemotherapy for cancer treatment. Clinical manifestations can vary from life-threatening arrythmias to chronic conditions, such as heart failure or hypertension, which dramatically reduce quality of life of cancer survivors. Standard chemotherapy exerts its toxic effect mainly by inducing oxidative stress and genomic instability, while new targeted therapies work by interfering with signaling pathways

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… common molecular alterations are a somatic G>T mutation in position 1849 of exon 14 of the Janus Kinase 2 ( JAK2 ) with valine to phenylalanine substitution in codon 617 (V617F); a W>L/K/A substitution in exon 10, codon 10 of the thrombopoietin receptor ( MPL ) gene; and mutations in exon 9 of the calreticulin …

Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28-29 2017, Doha, Qatar).

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called "living drugs". Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017),

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… The assembly of newly synthesized HLA class I heavy chain molecules with β2-microglobulin (β2-m) and tumor antigen-derived peptides is assisted by transient interactions with calnexin, calreticulin, ERp57 and tapasin [ 33 ]. …

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc

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… Induction of ER stress could also be the underlying reason for the increase in localization of calreticulin (CRT) in the cell membrane following TTFields exposure ( Voloshin et al., 2020a ). Mitochondria are another important organelle that could be affected by TTFields. …

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics.

Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40⁻50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patient

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… Calreticulin exposure dictates the immunogenicity of cancer cell death Nat. Med. 2007 13 54 10.1038/nm1523 17187072 96. Terenzi A. Pirker C. Keppler B.K. Berger W. Anticancer metal drugs and immunogenic cell death J. Inorg. Biochem. 2016 165 71 79 10.1016/j.jinorgbio.2016.06.021 27350082 97. …

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, the high resistance has become the most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), the light chain of major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one of the key mechanisms underlying tumor immunotherapy resistance. Therefore, eluci

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… In the ER, human leukocyte antigen-I (HLA-I), B2M, endoplasmic reticulum protein 57 (ERp57), Tapasin, and calreticulin collectively form a peptide-loading complex (PLC), facilitating the folding of the MHC-1α chain and obtaining mature MHC-I complex ( 33 ). …

Mesenchymal stem/stromal cells in cancer therapy.

The multipotent mesenchymal stem/stromal cells (MSCs), initially discovered from bone marrow in 1976, have been identified in nearly all tissues of human body now. The multipotency of MSCs allows them to give rise to osteocytes, chondrocytes, adipocytes, and other lineages. Moreover, armed with the immunomodulation capacity and tumor-homing property, MSCs are of special relevance for cell-based therapies in the treatment of cancer. However, hampered by lack of knowledge about the controversial roles that MSC plays in the crosstalk with tumors, limited progress has been made with regard to tran

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… Sequential interferon β-cisplatin treatment enhances the surface exposure of calreticulin in cancer cells via an interferon regulatory factor 1-dependent manner. Biomolecules. 2020;10(4). 10.3390/biom10040643 PMC7226424 32326356 133. …

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.

Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to

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… Similar results have been obtained in patients with calreticulin-mutated ET and MF ( 28 ). IFN treatment resulted in transfusion independence, decreased spleen size, and improved symptoms and quality of life in a significant proportion of MPN patients ( 29 ). …

Strategies to Improve Sensitivity to Radiotherapy in Pediatric Solid Tumors.

The primary goal in the treatment of pediatric malignancies is to maintain effective cancer control while minimizing toxicities and late effects. Radiotherapy is a component of standard therapy against many pediatric cancers, but tumor cell DNA damage repair mechanisms and the hypoxic tumor microenvironment may limit the effectiveness of this modality. Additionally, irradiated cancer cells often acquire resistance to radiotherapy that permits cancer cell survival or stimulates tumor regrowth after treatment, further limiting the efficacy of radiotherapy. Various preclinical studies have invest

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… Radiotherapy has also been shown to activate immunogenic cell death (ICD) [ 39 ] characterized by cell surface translocation of calreticulin, high-mobility group box 1 (HMGB1) release, and adenosine triphosphate (ATP) release. …

Thirty years from FDA approval of pegylated liposomal doxorubicin (Doxil/Caelyx): an updated analysis and future perspective.

In 2025, it will be 30 years since the initial clinical approval of pegylated liposomal doxorubicin (PLD) by the Food and Drug Administration. PLD predated the field of nanomedicine and became a model nanomedicine setting key pharmacological principles (prolonged circulation, slow drug release and the enhanced permeability and retention (EPR) effect) for clinical application of other nano-drugs in cancer therapy. The impressive reduction of cardiotoxicity conferred by PLD is the most valuable clinical asset. While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breas

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… (IL)-1 and IL-18. 102 Doxorubicin is now known to cause immunogenic cell death via pyroptosis as well as direct effects on both innate and adaptive immunity. 103 104 Immunogenic cell death is a unique form of cell death where immunostimulatory molecules such as damage-associated molecular patterns, calreticulin …

Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, inclu

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… Calreticulin exposure dictates the immunogenicity of cancer cell death . J. Nat. Med. 2007 , 13 , 54 – 61 . 10.1038/nm1523 . 17187072 Frega G. ; Kepp O. ; Turchetti D. ; Rizzo A. ; Pantaleo M. A. ; Brandi G. …

Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen

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… Hallmarks of ICD include externalization of Calreticulin, and Heat shock protein 90 (HSP90) and HSP70, externalization and later release of High mobility group box 1 (HMGB1), and release of ATP. ER, endoplasmic reticulum; UPR, unfolded protein response; ADC, antibody–drug conjugate. 2.2. …

Boosting Immunity against Multiple Myeloma.

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residua

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… Specifically, they found that in vitro exposure to bortezomib therapy resulted in an activation of DCs through calreticulin and engulfment of myeloma cells. The importance of the immune system was further validated in vivo and through single cell analysis using samples from myeloma patients [ 47 ]. …

Dendritic cell biology and its role in tumor immunotherapy.

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovere

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… Before being loaded to MHC-I molecules, the peptide must be trimmed by ER aminopeptidase (ERAP) chaperones, such as calnexin and calreticulin [ 53 ]. …

Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with part

Tumor-derived systems as novel biomedical tools-turning the enemy into an ally.

Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological

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… Moreover, CFIN induced immunogenic cell death (ICD), promoting the expression of calreticulin and stimulating DC phagocytosis. …