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Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy.

After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field. The appearance of immunotherapy, especially immune checkpoint inhibitors, has improved both the overall survival and quality of life of patients, many of whom are diagnosed late when classical treatments are ineffective. Despite these unprecedented results, a high percentage of patients do not respond initially to treatment or relapse after a period of response. This is due to resistance mechanisms, which require unde

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… The first drug approved by the FDA with this indication was pembrolizumab, an anti-PD-1 antibody used to treat patients with unresectable metastatic solid tumors with microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (dMMR). …

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) ba

Integrating CRISPR/Cas technology with clinical trials: Principles, progress and challenges.

CRISPR represent a groundbreaking genome-editing technology that has revolutionized genetic modification. This innovative tool offers an unparalleled revolution in the future treatment of genetic disorders, neurological diseases, infectious diseases and cancer. Despite the rapid expansion of CRISPR applications, its clinical use in humans is still relatively limited, with only 69 active clinical trials and 6 completed studies reported so far. This review examined current clinical trials and their processes in addressing various diseases via the CRISPR/Cas system. While earlier literatures have

BATF2 является регулятором интерферона β, сигнализирующего в астроцитах во время нейроинфламмации.

Астроцитический интерферон (IFN) (IFN) (информация) связан с уменьшением нейроинфламмации; однако эффекторы вниз по течению, ответственные за регулирование этой защиты, неизвестны. Здесь мы идентифицируем удельный коэффициент транскрипции IFN, основной коэффициент транскрипции лейцина АТФ-подобный АТФ2, который играет ключевую роль в модулировании последствий ITFN, сигнализирующих в астроцитах. Последовательность иммунопреобразования Хроматина показала, что НИМФ2 связывает и предотвращает перевыражение регулятивных факторов IFN (IRF)1 и IRF1, таких как caspase-1. Мы также показываем, что мыши

Follow-up of patients with mycosis fungoides after interferon α2b treatment failure.

IntroductionTreatment of T cell cutaneous lymphoma( CTCL) is a controversial subject and the effectiveness of treatment is still low.AimReport of single center experience of management CTCL after progression after first line treatment.Material and methodsWe present 41 patients with CTCL, 29 received interferon α2b in first line, and 12 of them received second line therapy.ResultsOverall response rate for second line therapy was 60%.ConclusionsResults of the follow-up of patients with mycosis fungoides after interferon α2b treatment failure with the literature review and discussion.

Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following th

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… One of the proposed mechanisms for this is through tumour cells’ intrinsic DNA mismatch repair mechanisms and the upregulation of specific drug-resistant proteins following long-term exposure to the chemotherapeutic agent. …

Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of t

Hallmarks of ribosomopathies.

Ribosomopathies are diseases caused by defects in ribosomal constituents or in factors with a role in ribosome assembly. Intriguingly, congenital ribosomopathies display a paradoxical transition from early symptoms due to cellular hypo-proliferation to an elevated cancer risk later in life. Another association between ribosome defects and cancer came into view after the recent discovery of somatic mutations in ribosomal proteins and rDNA copy number changes in a variety of tumor types, giving rise to somatic ribosomopathies. Despite these clear connections between ribosome defects and cancer,

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… Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency . Gastroenterology . 2014 ; 147 : 595 – 598 . 24941021 10.1053/j.gastro.2014.06.009 PMC4155505 31. …

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the

Janus kinase inhibition in the treatment and prevention of graft-versus-host disease.

Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For many years, corticosteroids have been the mainstay treatment for GVHD, but cases of steroid-refractory GVHD and the severe adverse effects of high-dose corticosteroids have increased the need for preventative and therapeutic strategies for GVHD. Due to the nature of alloreactive T cells, GVHD is inherently linked to the graft-versus-leukemia (GVL) effect, the therapeutic driving force behind stem cell transplantation. A considerable clinical ch

Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.

Chimeric antigen receptor (CAR)-T cell therapies represent a promising therapeutic approach for refractory autoimmune diseases. Although autologous CAR-T cells have achieved success thus far, they require expensive, individualised manufacturing, limiting their commercialisation potential. Allogeneic alternatives could overcome these scalability barriers, providing 'off-the-shelf' treatments, although they raise the issues of graft-vs-host reactions and host-mediated rejection. To mitigate such risks, gene-edited αβ T cells or non-alloreactive host cells (e.g., NK cells, γδ T cells) may be used

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Natural killer (NK) cells are potent anti-tumor and anti-microbial cells of our innate immune system. They are equipped with a vast array of receptors that recognize tumor cells and other pathogens. The innate immune activity of NK cells develops faster than the adaptive one performed by T cells, and studies suggest an important immunoregulatory role for each population against the other. The association, observed in acute myeloid leukemia patients receiving haploidentical killer-immunoglobulin-like-receptor-mismatched NK cells, with induction of complete remission was the determinant to begin

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms

Role of Cyclin-Dependent Kinase Inhibitors in Endometrial Cancer.

Endometrial Cancer (EC) is an important cause of death in women worldwide. Despite early diagnosis and optimal treatment of localized disease, relapsed patients have few therapeutic options because after first line therapy, currently no standard of care exists. On the basis of endocrine positivity of most endometrioid ECs, Endocrine Therapy (ET) is a reasonable and widely accepted option. Better knowledge of molecular mechanisms involved in cancer highlighted the deregulated activity of Cyclin-Dependent Kinases (CDKs) in the cell cycle as a hallmark of carcinogenesis supporting the development

Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complica

Highlighting recent achievements to advance more effective cancer immunotherapy.

From 17 to 19th October 2024, the XXI Italian Network for Bio-Immunotherapy of Tumors Meeting (NIBIT) took place in Palermo, in the marvelous historical location of Teatro Politeama, under the auspices of the Italian Association of Medical Oncology (AIOM), Italian Association of Cancer Research (AIRC), Fondazione Pezcoller, Italian Alliance against Cancer (ACC), Italian Lymphoma Foundation (FIL), Grazia Focacci Foundation and Melagioco Foundation. The conference covered a spectrum of topics ranging from target discovery to therapeutic advances in immuno-oncology, bringing world-renowned expert

Новое применение XPO1 для лечения миэлофиброза.

Myelofibrosis (MF) — новообразование, характеризующееся конституционными симптомами, прогрессивными цитопентиями и селеногамели. В основе патобологии MF лежит активация мутации на пути JAK/STAT и регулирование цитокинового костного мозга. Хотя многие ингибиторы JAK в настоящее время официально утверждены и обеспечивают значительное улучшение симптомов, эти агенты не имеют курса на изменение потенциала. Кроме того, результаты являются неудовлетворительными для пациентов, которые не справляются с ингибиторами JAK, что подчеркивает необходимость применения новых методов лечения, основанных на исп

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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… Enhanced resistance of CD133 + brain tumor stem cells to chemotherapeutic agents such as paclitaxel, carboplatin, etoposide, and temozolomide have been attributed to higher expression of ABCG2, increased activity of DNA mismatch repair genes, and an altered balance of intracellular pro-/anti-apoptotic …

Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma.

Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells (APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppre

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra