Glioblastoma (GBM) are the most prevalent type of primary malignant brain tumor in adults that can develop in the brain stem, cerebellum, or spinal cord. Temozolomide (TMZ) is an alkylating agent that is used to treat adults with newly diagnosed GBM and resistant anaplastic astrocytoma who have progressed on a nitrosourea and procarbazine-containing therapy regimen. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioblastoma therapy. Cell membrane damage produced by mechanisms such as intracellular iron build-up, reactive oxygen species (ROS), lipid peroxidation, glutathione peroxidase (GPX) activity failure, and x-catenin (xCT) causes ferroptosis (iron dependent programmed cell death). This blog discusses the molecular mechanisms of ferroptosis, its application, and challenges in the development and treatment of glioblastoma. GBM invasiveness and treatment resistance may increase if ferroptosis is avoided due to changes in glucose, lipid, glutamine, and iron metabolism. Targeting ferroptosis, which involves fatal phospholipid peroxidation due to dysregulated redox homeostasis and cellular metabolism, could be a promising treatment for GBM, as it is essential for tumor cell viability.
Cardiovascular disease continues to be a major concern, and the electrocardiogram (ECG) is a proven non-invasive technique for detecting cardiac issues. Traditional diagnosis, on the other hand, is based on an individual patient’s medical history and clinical examinations, which are ineffective owing to diverse data. By analyzing the electrical activity of the heart, AI is being used to identify prognostic arrhythmias such as atrial fibrillation. Deep convolutional neural networks (CNNs) are the basic building blocks of machine learning algorithms used in cardiovascular medicine to analyze ECG data. The adoption and use of AI-based diagnostic tools in clinical settings, however, may be limited by issues with interpretability and openness, such as evaluating models’ performance across datasets, processing power consumption, privacy and security concerns, imbalanced and limited datasets, and lack of clear guidelines for CNNs. Nevertheless, these technologies offer standardization, continuous, real-time monitoring, and more accurate interpretation—all of which have the potential to improve patient outcomes. This blog provides an overview of AI technologies applied and the challenges associated with the ECG in the diagnosis of cardiovascular diseases.
Breast cancer is a diverse disease with varying clinical presentations, morphologic features, and molecular characteristics. It is influenced by various genetic pathways and is a major trend in breast cancer care. Neoadjuvant chemotherapy is a major trend, requiring integrated multidisciplinary care from pathologists, radiologists, surgeons, and oncologists. Anti-HER2 therapy has improved clinical results for HER2-positive breast cancer patients.
Pertuzumab, a humanized monoclonal antibody, targets the extracellular dimerization domain of HER2, inhibiting downstream signaling and cell survival pathways. It is used in conjunction with trastuzumab and docetaxel to treat HER2-positive metastatic breast cancer. In addition to directly encouraging the death of cancer cells, monoclonal antibodies also trigger immunological activation, which is deadly to tumour cells.
Pertuzumab possesses the capability to elicit immune effector responses, including cell-mediated cytotoxicity that is dependent on antibodies. The antibody targets the PI3K/AKT and RAS/MEK/ERK pathways, protecting normal cells from suicide. It can activate immunological effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity. Trastuzumab and pertuzumab function in complementary ways, highlighting the importance of understanding the biology of this devastating disease. This blog focuses on the mechanism of pertuzumab in patients with early-stage HER2-positive breast cancer receiving neoadjuvant treatment.
In this blog, our focus would be on autosomal dominant disorders and autosomal recessive disorders that can be cured with a gene therapy approach. Gene therapy has faced numerous obstacles and it took an extensive period of time for reaching up to the clinic from the research lab. However, continuous and rapid advancement in the molecular biology and genomics field set the stage to develop gene therapies for a range of inherited disorders. Because of the certain limitation of the application of drug and surgical treatment, some of the cardiovascular disease also needed gene therapy approaches. Though huge progress has been observed in the treatment of autosomal recessive disorders by delivering the normal exogenous genes that can restore the proper biological function of the affected or mutated gene. However, a similar outcome cannot be expected in the case of autosomal dominant disorder as precise differentiation is required between diseases/mutated alleles from that of healthy/unaffected alleles.
Constant emergence of new gene therapies as well as refinement of the existing ones changes the global landscape of the cell and gene therapies clinical trials, where the US, China, and Europe are leading in respect of the number of trials conducted. As per Global Data, China showed 15% faster growth in cell and gene therapy clinical trials making the Asia-Pacific region contributes for one-third of the trial activities. As a result, the Asia Pacific region is witnessing 50% faster growth than the rest of the world (ROW). Asia Pacific region leads globally in terms of CAR-T cell gene therapy clinical trials for the time period 2015-2022 since China alone conducted ~60% of all CAR-T trials. Till April 2022, there are 19 approved gene therapies, 17 RNA-approved therapies while 56 non-genetically modified approved cell therapies (Figure 1). Details of the approved location of the clinical trials of gene therapies and RNA therapies drug product are provided in Table No.1 and Table No. 2 respectively, which presents a bird’s-eye view of the landscape of the clinical trials of the approved gene and RNA therapies.
Quite often we hear people talking about microbiome disturbance leading to unhealthy aging and going back to our ancestral habits including paleo diet has the potential to cure many diseases. This folk wisdom is supported by some recent scientific publications. However, we have majorly neglected the fact that paleo diet-eating and cave-dwelling ancestors of ours had several insects on their bodies, and inside caves, they constantly fought with insects. Thus we argue, if modern habits are responsible for the current epidemic of metabolic/cardiovascular/neurological and other degenerative diseases, may be insects also had some role to play in the healthier aging of our ancestors as compared to us. In this blog post, we would like to review the benefits of insect bitings/stings published in the literature. Thus we will examine, if an apparent parasitic interaction between humans and insects is a mutualistic relationship in disguise. When an insect bites/stings us, it releases a barrage of biologically active compounds, including those with potential to act as anticoagulant/vasodilator. Can these chemicals be exploited to cure Cardio-Vascular-Diseases/dissolve internal blood clots? More importantly, there are other chemicals which have virucidal, anti-cancer and antimicrobial properties, which in either native or modified form can be repurposed for pharmaceutical applications.
Therapeutic agents in cancer treatment are aimed at rapidly dividing cells, limiting their multiplication, and promoting apoptosis. The lack of selectivity of these conventional methods resulted in needless damage to normal cells leading to severe adverse effects. Nanotechnology in medicine gratifies the constraint in conventional treatment by delivering conventional drugs to the targeted tissue or organ and plays an important role in targeting the delivery, thereby avoiding systemic toxicity and increasing the bioavailability and therapeutic index of the drug. The advantage of using nanoparticles as drug carriers are in their binding competence and reversing multidrug resistance. Using active and passive targeting strategies, nanoparticles enhance intracellular drug concentrations. The present review focuses the on the basic pathophysiology of cancer and the various types of nanoparticulate drug delivery systems that have been explored so far, taking advantage of the tumor vasculature and other molecular mechanisms which differentiates cancer cells from normal ones, for the delivery of anticancer therapeutics for effective management of cancer. The article also aims to focus on the various surface-engineered nanoparticles for the targeted delivery of cancer.
Moving ahead with our blog series we are bringing up Base Editing a new feather in the cap of gene editing therapy. Base Editing Therapy is a technology that introduces single-nucleotide variants (SNVs) precisely and efficiently at targeted genomic sequences without causing double-stranded breaks in the DNA enabling it as an efficient technique of genome editing. Nearly half of known pathogenic genetic variants are due to SNVs and base editing therapy holds enormous potential for the treatment of these genetic disorders by either temporary RNA or permanent DNA base alterations. Correction of single point mutations will be a major point of interest in the upcoming times for the scientific community for precision medicine.
In the journey of our Cancer Immunotherapy blog series, let us introduce CAR-T cell therapy, another milestone in recent years in the field of immunotherapy that has revolutionized the modern medicine. Chimeric Antigen Receptor (CAR) T cell therapy utilizes T-cells, a type of white blood cell (immune cells), to fight cancer by engineering them ex vivo prior to infusing back into the patient. These CAR T-cells can specifically find and destroy cancerous cells. CAR T-cell therapy is a type of cell-based gene therapy or Adoptive Cell Therapy (ACT) as it involves gene alteration of T-cells that enables them to attack specific cancer cells.
The Indian pharmaceutical industry has seen an exponential growth in the field of fill finished dosage forms, especially generics but the future lies beyond generics in the field of complex generics, biosimilairs, vaccines and New Chemical Entities (NCE)/New Biological Entities (NBE). Developing NCEs and NBEs will position Indian companies in the ivy league of global innovators. Risk adverseness, lack of perseverance and complex, long regulatory approval process are impeding Indian pharma companies to venture into NCE/NBE research. Product portfolio expansion into complex generic injectables is an attractive high-return alternative for the Indian generic pharmaceutical industries.