Current Cancer Therapy Reviews - Online First

Colorectal cancer (CRC) ranks among the most prevalent malignancies globally, driven by a complex interplay of genetic, molecular, and environmental factors. Dostarlimab, a humanized monoclonal antibody targeting the programmed cell death protein-1 (PD-1) receptor, has emerged as a breakthrough immunotherapy for CRC, particularly in mismatch repair-deficient (dMMR) subtypes. Its ability to enhance anti-tumor immune responses has positioned it as a promising therapeutic agent, with ongoing research exploring its efficacy across CRC subtypes and in combination therapies.

This study investigates the therapeutic potential of Dostarlimab in CRC management by analyzing scientific data collected from various literature databases, including Google Scholar, Scopus, and PubMed. The review encompasses the genetic and molecular underpinnings of CRC, such as mutations in APC, KRAS, and TP53, and the regulatory roles of non-coding RNAs (ncRNAs). Detailed pharmacological mechanisms, clinical trial outcomes, and comparative efficacy of Dostarlimab against other immunotherapies were evaluated to assess its biological and clinical significance. Analytical aspects of Dostarlimab’s pharmacokinetics and pharmacodynamics were also explored.

Scientific data analysis underscores the pivotal role of Dostarlimab in CRC treatment, particularly for dMMR/MSI-H subtypes, where it achieved a 100% clinical complete response rate in a phase II trial for locally advanced rectal cancer. The drug’s mechanism involves PD-1 inhibition, enhancing T-cell-mediated tumor destruction. Genomic aberrations (e.g., KRAS, BRAF, TP53 mutations) and ncRNAs (e.g., miRNAs and lncRNAs) were identified as key influencers of CRC prognosis and potential therapeutic targets. Dostarlimab exhibits significant efficacy in dMMR/MSI-H CRC, with ongoing trials assessing its impact on mismatch repair-proficient (pMMR) subtypes. Its favorable pharmacokinetic profile (e.g., half-life of 25.4 days) and tolerable safety profile further enhance its clinical utility. Comparative studies with pembrolizumab and nivolumab highlight Dostarlimab’s superior response rates in specific CRC cohorts.

The scientific data from this review affirm the transformative potential of Dostarlimab in CRC management, offering hope for improved outcomes through personalized immunotherapy. Its integration with genetic and molecular insights paves the way for targeted CRC therapies.

Over the past two decades, cancer has emerged as a major global health concern, affecting a significant portion of the population. While chemotherapeutic agents have revolutionized cancer treatment, they have also introduced a range of adverse effects, with neurotoxicity being a critical complication that can severely limit treatment options.

This review aims to provide a comprehensive analysis of the mechanisms underlying chemotherapy-induced neurotoxicity and to identify strategies for mitigating its effects.

A comprehensive bibliographic investigation was conducted using scientific databases such as PubMed, Scopus, Web of Science, SciELO, NISCAIR, and Google Scholar. The search included peer-reviewed articles published in English up to December 2024, focusing on the neurotoxic effects of chemotherapy on the central nervous system (CNS). Keywords included “chemotherapy,” “neurotoxicity,” “CNS toxicity,” “oxidative stress,” “neuronal apoptosis,” “hippocampus toxicity,” “cortical toxicity,” “CNS syndromes,” and “neuroinflammation.” Inclusion criteria were studies that reported mechanistic insights, clinical observations, and experimental findings on chemotherapy-induced CNS toxicity. Relevant articles were screened based on title and abstract, followed by a full-text evaluation to extract key data and identify patterns in neurotoxic mechanisms and clinical manifestations.

Patients with underlying conditions such as diabetes, hereditary neuropathies, or previous exposure to neurotoxic agents are particularly susceptible to chemotherapy-induced peripheral and central neurotoxicity. Identified mechanisms include microglial activation, neuronal apoptosis, demyelination, and oxidative stress, especially affecting cortical and hippocampal regions. These processes contribute to cognitive and functional impairments that manifest as transient or progressive neurological symptoms, including cognitive deficits, aphasia, hemiparesis, and dementia. Differentiating these effects from cancer progression remains a clinical challenge and may result in diagnostic delays or treatment errors.

Establishing a clear mechanistic understanding of chemotherapy-induced neurotoxicity is essential for advancing therapeutic strategies that minimize adverse effects. Enhanced knowledge of underlying biological pathways will support the development of neuroprotective interventions and improve patient management outcomes in oncology settings.

Cancer is a complex disease caused by genetic mutations and external factors like radiation and lifestyle choices. Traditional treatments, including chemotherapy and radiation, often cause severe side effects, prompting interest in alternative therapies. Herbal remedies, rich in phytochemicals, have shown promise in cancer prevention and treatment by targeting tumor growth, inducing apoptosis, and inhibiting angiogenesis and metastasis. This review article aims to explore and analyze the potential of herbal remedies in cancer treatment, focusing on their mechanisms of action, including apoptosis induction, inhibition of angiogenesis, and modulation of molecular pathways.

This review examines key phytochemicals curcumin, naringenin, capsaicin, and resveratrol for their anticancer properties. Relevant studies were analyzed to assess their mechanisms of action, such as apoptosis induction, inhibition of molecular pathways like COX-2 and 5-LOX, and protective effects on healthy cells. A literature search was conducted using databases such as PubMed, Scopus, and Web of Science. Keywords included “phytochemicals,” “herbal,” “curcumin,” “naringenin,” “capsaicin,” “resveratrol,” “herbal remedies,” and “cancer therapy.” Studies published in peer reviewed journals over the past 30 years were selected. The quality of the literature was assessed based on study design, sample size, reproducibility, and relevance to cancer treatment.

The findings highlight that these phytochemicals exert significant anti-cancer effects by inducing cell cycle arrest and apoptosis while inhibiting angiogenesis and metastasis. For example, curcumin and resveratrol inhibit cancer progression by targeting key molecular pathways. Additionally, herbal remedies protect healthy cells from damage often caused by chemotherapy and radiation, making them an attractive alternative or complementary option for treatment.

These phytochemicals demonstrated significant therapeutic potential through multi-targeted actions, such as apoptosis induction, angiogenesis inhibition, and protection of healthy cells. Their ability to complement conventional therapies, highlights the relevance of integrating herbal remedies into cancer management strategies.

Herbal remedies, with their potent phytochemicals, offer a promising alternative to cancer therapy, providing protective effects to normal cells while targeting cancerous ones. Their lower toxicity compared to conventional treatments suggests they could play a crucial role in future cancer therapies. However, further clinical research is needed to establish optimal dosages and treatment protocols for effective integration into cancer care.

Lung cancer remains a leading global health crisis, with benzo[a]pyrene (B[a]P) from cigarette smoke identified as a primary carcinogen. This study investigated the microbial biotransformation of ginsenoside Rg1 into dihydroprotopanaxatriol (DHPPT) by Curvularia lunata NRRL 2178 and evaluated its protective effects against B[a]P-induced pulmonary toxicity through comprehensive biochemical and histological analyses.

DHPPT was produced via C. lunata fermentation of Rg1, isolated by n-butanol extraction and column chromatography, and characterized using FT-IR and ¹H-NMR spectroscopy. Cytotoxicity was assessed against A549 cells (MTT assay). In vivo studies involved plasma lipid analysis (TC, TG, and HDL-C), lung oxidative stress markers (GSH, CAT, GPx, and MDA), inflammatory mediators, including IL-6, NF-κB, and matrix metalloproteinases (MMP-2 & MMP-12), and NADPH oxidase gene expression (NOX-2, NOX-4). Moreover, histopathology was performed using H&E staining.

DHPPT showed potent anticancer activity (IC50 = 67.66 μg/mL) with low toxicity (LD50 = 780 mg/kg). In B[a]P-exposed mice, DHPPT (39 mg/kg) significantly increased HDL-C (87.5%) and antioxidant markers (GSH 162%, CAT 74.6%, GPx 79.8%), decreased TC (28.9%), TG (26.7%), and MDA (60.5%), reduced inflammatory markers (IL-6 32.9%, NF-κB 36.0%, MMP-2 53.3%, MMP-12 40.5%), and downregulated NOX-2 (52.7%) and NOX-4 (63.5%). Histopathology revealed a preserved alveolar structure with reduced inflammation.

The therapeutic effects of DHPPT involve multiple mechanisms, such as antioxidant activity through increased GSH, CAT, and GPx levels enhanced free radical scavenging, while decreased MDA indicated reduced lipid peroxidation. Anti-inflammatory action via reduced IL-6 and NF-κB suppressed cytokine signaling pathways, while decreased MMP-2/MMP-12 limited tissue remodeling. Additionally, NOX-2/NOX-4 downregulation reduced reactive oxygen species generation. The superior efficacy of DHPPT against tamoxifen suggests its unique ability to simultaneously target oxidative stress, inflammation, and genetic pathways disrupted by B[a]P. Furthermore, the biotransformation by C. lunata enhanced bioavailability by removing glucose moieties, while preserving the active aglycone structure.

DHPPT demonstrates significant chemopreventive potential against B[a]P-induced lung damage through coordinated antioxidant, anti-inflammatory, and gene-regulatory mechanisms. These findings support further development of microbial-transformed ginsenosides as multifaceted therapeutic agents, with future studies needed to evaluate clinical applications and potential synergies with conventional treatments.

Cancer-associated venous thromboembolism (VTE) presents a complex clinical challenge, with the need to balance effective anticoagulation against the risk of bleeding. Direct oral anticoagulants (DOACs) offer convenience but their efficacy and safety in this context remain debated. This systematic review and meta-analysis endeavor to evaluate the effectiveness and safety of DOACs in managing VTE associated with cancer. The findings offer essential perspectives to guide clinical decision-making.

We performed an exhaustive search across electronic databases such, as PubMed, EMBASE, and the Cochrane CENTRAL, spanning from their inception to December 15, 2023. Only English-published articles evaluating the effectiveness and safety of DOACs in managing cancer-associated VTE were considered. Evaluation criteria encompassed recurrent VTE, major bleeding (MB), clinically significant non-major bleeding (CSNMB), and clinically relevant bleeding (CRB). Statistical analyses were conducted utilizing Comprehensive Meta-Analysis software.

From the 1195 records, 8 studies with 3913 patients were included. DOACs demonstrated a significant reduction in recurrent VTE risk (OR: 0.73, CI 95%: 0.57-0.93, p =0.01) compared to traditional anticoagulants. However, there was a marginal increase in MB risk (OR: 1.24, CI 95%: 0.90-1.69, p =0.17) with DOACs, though not statistically significant. Notably, DOACs were associated with a higher risk of CRNMB (OR: 1.64, CI 95%: 1.24-2.17, p <0.001) and CRB (OR: 1.22, CI 95%: 1.00-1.52, p =0.04). No publication bias was observed. Gastrointestinal cancer, Rivaroxaban/apixaban use, switching from dalteparin, improved physical function with DOACs, specific tumor sites, and older age subgroups were predictors for bleeding complications in cancer patients on anticoagulant therapy.

This meta-analysis provides evidence supporting the efficacy of DOACs in reducing VTE recurrence in cancer patients. However, the increased risk of bleeding complications warrants careful consideration in personalized treatment decisions. Ongoing research is necessary to refine therapeutic strategies in this complex clinical landscape.