Clinical Cancer Drugs - Volume 11, Issue 1, 2025

The EGFR, a major receptor tyrosine kinase in the HER family, controls cell growth and division via its extracellular and intracellular tyrosine kinase domains. Ligand binding and receptor dimerization stimulate downstream pathways such as KRAS-BRAF-MEK-ERK, which are critical for cell proliferation, survival, and angiogenesis. Dysregulation of EGFR is linked to cancer development by encouraging uncontrolled cell proliferation, resistance to apoptosis, and metastases. Anti-EGFR medicines, including monoclonal antibodies (e.g., cetuximab) that prevent ligand binding and tyrosine kinase inhibitors (e.g., gefitinib), suppress abnormal EGFR signaling to slow cancer growth. Their usefulness is, however, constrained by issues, such as drug resistance, off-target effects, and limited potency in specific tumors. By using nanoparticles, including liposomes, polymeric nanoparticles, and quantum dots, for accurate drug administration, decreased systemic toxicity, and circumvention of resistance mechanisms, nanotechnology-based techniques have been developed to improve EGFR-targeted therapy. Functionalized nanoparticles improve effectiveness and make combo treatments possible by permitting regulated drug release and active targeting. These developments hold promise for addressing present constraints and offering individualized treatment choices. Comprehending EGFR signaling and using nanotechnology continue to be essential for creating more potent, focused cancer treatments.

Proton pump inhibitors (PPIs), commonly utilized for the management of acid-related disorders, are gaining attention for their repurposing potential in oncology, particularly due to their ability to modulate the acidic tumor microenvironment and disrupt proton transport mechanisms. Beyond their primary role in gastric acid suppression, PPIs exhibit a spectrum of anticancer activities, including inhibition of vacuolar-type H⁺-ATPase (V-ATPase), disruption of proton gradients, and interference with tumor metabolic adaptation. These effects contribute to increased lysosomal and endosomal pH, impairing autophagic flux, inducing apoptosis, and reducing cancer cell proliferation. Preclinical evidence suggests that PPIs can augment the effectiveness of conventional cancer treatments, such as chemotherapy and immunotherapy, through mechanisms like intracellular modulation of the acidic tumour microenvironment, inhibition of acidic vesicle sequestration, and suppression of efflux transporters (e.g., P-glycoprotein [P-gp], MRP1, BCRP). Furthermore, PPIs offer a promising strategy to counteract drug resistance, a significant challenge in cancer therapeutics. By targeting metabolic reprogramming pathways such as fatty acid synthase (FASN) and TOPK signaling, PPIs impair tumor survival mechanisms, enhance chemotherapy sensitivity, and restore drug efficacy in resistant cancer types. Although the precise molecular pathways responsible for these anticancer effects remain under investigation, the repurposing of PPIs as adjuncts in oncological regimens holds considerable promise. Emerging strategies, including artificial intelligence (AI)-driven drug repurposing, multi-omics biomarker identification, and nanomedicine-based PPI delivery, are expected to optimize their clinical applications. Ongoing and future studies should aim to unravel these molecular mechanisms in greater detail and prioritize clinical trials to evaluate their therapeutic efficacy. This repurposing approach could facilitate the development of innovative strategies to optimize cancer treatment and improve patient outcomes.

Durvalumab, the programmed death-ligand 1 (PD-L1) targeting monoclonal antibody, has revolutionized the treatment of numerous cancers, such as Non-Small Cell Lung Cancer (NSCLC). Despite producing remarkable clinical advantages, immune-related toxicities, i.e., pneumonitis and colitis, are being closely monitored and must be treated on an individual basis. The safety profile, including immune-related toxicities, must be carefully considered. The role of Durvalumab as a consolidative treatment for unresectable stage III NSCLC, as demonstrated in the PACIFIC trial, marked a significant milestone in the adoption of immunotherapy. However, recent findings suggest that its benefit varies among patient subgroups, highlighting the need for more precise biomarkers beyond PD-L1 expression. Ongoing trials, such as PACIFIC-9 and AEGEAN, are investigating durvalumab in different settings and combination therapies with an aim to overcome resistance mechanisms. The PACIFIC-9 is an example where durvalumab is being combined with the CD73-blocking anti-CD73 antibody oleclumab and the CD94/NKG2A-blocking monalizumab in unresectable stage III NSCLC patients who maintain a stable response through chemoradiotherapy. Early findings are encouraging, but phase III efficacy data remain awaited. Heterogeneity in treatment response between tumor types, including bladder carcinoma, head and neck cancers, and cholangiocarcinoma, is one reason why it is worth aiming for tumor-intrinsic and microenvironmental determinants of responsiveness to immunotherapy. Durvalumab is of landmark significance in a range of malignancies but needs further efforts in the characterization of resistance mechanisms, the optimization of combination strategies, and the development of predictive models for the guidance of personalised therapeutic regimens.

CAR-T cell therapy has transformed cancer treatment by harnessing genetically engineered T cells to specifically target and destroy cancer cells, especially in blood cancers like leukemia and lymphoma. Despite its success, challenges such as serious side effect cytokine release syndrome, neurotoxicity and the high cost of treatment hinder widespread access. Research is ongoing to broaden its use to solid tumors and improve its safety, effectiveness, and affordability. Future efforts will focus on refining CAR constructs, reducing adverse effects, enhancing manufacturing efficiency, and ensuring equitable access through regulatory cooperation, facilitating its wider adoption in precision oncology.

Utilizing the body's immune system to combat cancer has become a viable tactic known as cancer immunotherapy. Metallic nanoparticles, or MNPs, have drawn a lot of interest because of their special qualities and their uses in cancer immunotherapy. The manufacturing processes of MNPs, their function in altering the tumor microenvironment (TME), and their capacity to control immune cells for potent anticancer effects are all thoroughly covered in this review. The review underscores the benefits of MNPs in surmounting obstacles linked to traditional cancer treatments, including toxicity, resistance, and off-target effects. It also goes over the different ways that MNPs modulate the immune system, For example, by generating reactive oxygen species (ROS), reducing glutathione (GSH) levels, and improving hypoxia. The research also examines the ability of MNPs to enhance the maturation of dendritic cells, shift macrophages towards an M1 phenotype, stimulate T-cell responses, and aid in the transportation of natural killer (NK) cells. The investigation is focused on understanding the synergistic effects of MNPsIn conjunction with other immunotherapeutic approaches, such as checkpoint inhibitors and cell-based treatments, in order to generate potent immune responses against cancer.

In the realm of nanomedicine, graphene quantum dots (GQDs) stand at the forefront, offering transformative potential for cancer diagnosis and therapy. Possessing exceptional optical and electronic properties, biocompatibility, and versatile surface customization, GQDs emerge as powerful tools for advanced imaging and targeted drug delivery. Synthesized through innovative bottom-up and top-down methods, GQDs present a diverse tool for precise tailoring. Their application in cancer therapy, especially when functionalized with vitamins, proteins, peptides, and polysaccharides, showcases remarkable versatility and efficacy. These tailored drug delivery systems demonstrate not only enhanced drug effectiveness and reduced toxicity but also enable targeted cancer treatment. Ongoing research into GQD synthesis and functionalization, coupled with a deeper understanding of their interactions with biological systems, promises to further refine cancer diagnosis and therapy. The potential of GQDs as intelligent carriers holds the key to revolutionizing cancer treatment, offering renewed hope for improved patient outcomes and quality of life.

Despite the major advancements in cancer treatment, colon cancer (CC) is still one of the most lethal malignancies worldwide. Among various type of cancer, it is the third largest prevailing kind of cancer affecting both men and women equally. Metastatic development is particularly common in individuals with advanced stages and frequently associated with subpar response of chemotherapy and severe morbidity. The unfavorable effects of intense chemotherapy on normal cells and emergence of multidrug resistance are the two main reasons for treatment failure. Recent research in nanotechnology enables the use of advanced natural and synthetic biomaterials alone or in combination to target cancer cells with anticancer medications without affecting healthy cells. Anticancer drug laden nanocarriers improve the drug distribution, bioavailability and accumulation of cytotoxic therapeutic concentration at tumor site along with reduced side effects. Additionally, upon oral administration, polymeric vehicles shield the medication from premature release, degradation in upper gastrointestinal tract and facilitate controlled release at cancerous site of colon. Here, we primarily focus on the present situation and possible advantages of polymeric biomaterials either owned or in conjunction with other therapeutics to develop ideal drug carrier systems to treat colon carcinoma.