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Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

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… Among the best clinically characterized 4-anilinoquinazolines are gefitinib and erlotinib , selective ATP-competitive EGFR inhibitors used for NSCLC with common activating EGFR kinase-domain mutations, including exon 19 deletions (del19) and L858R [ 52 ]. … First-generation reversible inhibitors (e.g., gefitinib , erlotinib ) showed efficacy in tumors harboring activating EGFR mutations but were limited by the emergence of the T790M gatekeeper mutation, which increased ATP affinity and reduced inhibitor binding. …

Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.

Companion diagnostics (CDx) plays a pivotal role in precision medicine by enabling personalized treatment plans based on individual biomarker profiles. This approach can enhance therapeutic efficacy in selected indications and may reduce healthcare expenditures. Particularly in oncology, precision targeted therapies targeting pathways such as EGFR, HER2, and programmed death-1/programmed death-ligand 1 have established robust models for biomarker-driven treatment. However, rapid advancements in diagnostic technologies, expanding application scopes, and increasingly complex mechanisms of biomar

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… These discoveries have paved the way for the development of first‐generation EGFR tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib [ 82 ], followed by second‐ and third‐generation TKIs such as afatinib [ 83 ] and osimertinib [ 84 ], respectively. …

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

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… This resistance has been observed across a range of chemotherapy agents, such as doxorubicin, paclitaxel, gemcitabine, gefitinib, temozolomide, and platinum-based drugs, positioning ALDH as a critical marker for CSC-related drug resistance [ 60 ]. …

Drug-Induced Periocular and Ocular Surface Disorders: An EAACI Position Paper.

Various systemic and topical medications can induce ocular and periocular cutaneous adverse effects (AEs), ranging from mild to severe. These AEs may lead to ocular surface (OS) damage and, in some cases, life-threatening complications. Drug-induced ocular adverse reactions are generally classified into two primary categories: toxic reactions and/or allergic hypersensitivity reactions, which can be IgE or non-IgE-mediated. Systemic antibiotics, antivirals, and anticonvulsants can trigger adverse reactions that may involve the OS. Drugs like antihistamines, beta-blockers, antipsychotics, antide

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… C., Banuls J., Belinchon I., Blanes M., and Massuti B., “Trichomegaly Following Treatment With Gefitinib (ZD1839),” British Journal of Dermatology 151, no. 5 (2004): 1111–1112. 91. Joganathan V. and Norris J. …

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion has been identified as an oncogenic driver of various solid tumors, and it is rare in non-smalll cell lung cancer (NSCLC) with a frequency of approximately less than 1%. Next-generation sequencing (NGS) is of priority for detecting NTRK fusions, especially RNA-based NGS. Currently, the tropomyosin receptor kinase (TRK) inhibitors have shown promising efficacy and well tolerance in patients with NTRK fusion-positive solid tumors, regardless of tumor histology. The first-generation TRK inhibitors (larotrectinib and entrectinib) are reco

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… A NSCLC patient with EGFR 19del received gefitinib followed by osimertinib because of the emergence of EGFR T790M, then EGFR C797S and LMNA-NTRK1 fusion were detected when resisting to osimertinib. …

Impact of Glucocorticoid Use in Oncology in the Immunotherapy Era.

Thanks to their anti-inflammatory, anti-oedema, and anti-allergy properties, glucocorticoids are among the most widely prescribed drugs in patients with cancer. The indications for glucocorticoid use are very wide and varied in the context of cancer and include the symptomatic management of cancer-related symptoms (compression, pain, oedema, altered general state) but also prevention or treatment of common side effects of anti-cancer therapies (nausea, allergies, etc.) or immune-related adverse events (irAE). In this review, we first give an overview of the different clinical situations where

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… Certain types of chemotherapy (bleomycin, gemcitabine) [ 61 ] or targeted therapies, EGFR (erlotinib, gefitinib) [ 62 ], mTOR or MEK inhibitors [ 63 ], or even monoclonal antibodies targeting HER2 (especially certain new antibody-drug conjugates such as trastuzumab deruxtecan, known to cause interstitial …

Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection

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… Kundu ST Byers LA Peng DH The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers Oncogene 2016 35 2 173 186 25798833 10.1038/onc.2015.71 PMC4580489 33 Narita M Shimura E Nagasawa A Chronic treatment of non-small-cell lung cancer cells with gefitinib …

Семья гистона деацетилазы в здравии и болезни.

Классические деацетилазы, включая классы I, II и IV, в зависимости от цинка, повсеместно присутствуют у млекопитающих и играют жизненно важную роль в многочисленных биологических процессах. На сегодняшний день eleven Были выявлены члены < < хисттон деацетилаза > > , а именно < < хиттон деацетилаза > > . 1 через гистонную деацетилазу 11. Растущий объем данных подчеркивает важнейшую роль этих гистоновых деацетилазов как в физиологических, так и патологических условиях. В частности, эти гистонные деацетилазы участвуют в различных клеточных процессах, включая воспаление, ме

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… Overcame gefitinib resistance in non-small cell lung cancer. (PMID: 35188360) | In vitro, In vivo | Preclinical | 1. 50 nM, 25 mg/kg, 50 mg/kg (PMID: 35188360) Bisthianostat | Pan inhibitor | 1. … For instance, HDAC1 inhibition induces DUSP1 upregulation, inhibits EGFR signaling and resensitizes gefitinib-resistant NSCLC cells. 237 HDAC4 downregulation reduces STAT1 phosphorylation and EGFR expression, thereby contributing to doxorubicin sensitivity and promoting apoptosis in lung cancer. 238 …

Has the development of cancer biomarkers to guide treatment improved health outcomes?

During the last decade, testing the patient's biomarker status prior to the administration of corresponding co-dependent therapies has been emerging in clinical practice. These biomarker-guided therapies have promoted the promise of more personalized medicine, with the prescription of the right treatment to the right patient, while avoiding expensive ineffective drugs and adverse drug reactions. Cancer treatments have especially taken advantage of this technology. We assess how the introduction of biomarker tests guiding cancer therapy have affected the premature mortality and survival of canc

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… code | Drug generic name L01XC03 | Trastuzumab | x | x | x | | | | | | | L01XC06 | Cetuximab | | | | x | x | | | | | L01XC08 | Panitumumab | | | | x | x | | | | | L01XC13 | Pertuzumab | | x | | | | | | | | L01XC18 | Pembrolizumab | | | | | | | | | x | L01XE02 | Gefitinib …

Unraveling the Anticancer Effect of Curcumin and Resveratrol.

Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unr

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… gastric | [ 431 ] curcumin | 5-fluorouracil + oxaliplatin | colon | [ 432 ] curcumin | bevacizumab | liver | [ 433 ] curcumin | imatinib | leukemia | [ 434 ] curcumin | paclitaxel | brain | [ 435 ] curcumin | oxaliplatin | colorectal | [ 436 ] curcumin | temozolomide | glioblastoma | [ 437 ] curcumin | gefitinib …

Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

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… Triptolide inhibits epithelial-mesenchymal transition and induces apoptosis in gefitinib-resistant lung cancer cells. Oncol Rep. 2020;43:1569–1579. doi:10.3892/or.2020.7542 73. Tahara RK, Brewer TM, Theriault RL, Ueno NT. Bone metastasis of breast cancer. Adv Exp Med Biol . 2019;1152:105–129. 74. …

Radionuclide-labelled nanoparticles for cancer combination therapy: a review.

Radionuclide therapy (RT) is widely used to advanced local cancers. However, its therapeutic efficacy is limited to the radiation resistance of cancer cells. Combination therapy aims to circumvent tumor resistance, and the combination of RT with photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy (CMT), and immunotherapy has shown promising treatment outcomes. Nanotechnology holds promise in advancing combination therapy by integrating multiple therapies on a nanostructure platform. This is due to the increased surface area, passive/active targeting capabilities, high payload

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… Mucin-1 conjugated polyamidoamine-based nanoparticles for image-guided delivery of gefitinib to breast cancer. Int J Biol Macromol. 2021;174:185–97. 10. Viswanath D, Won Y-Y. …

The 8p11 myeloproliferative syndrome: Genotypic and phenotypic classification and targeted therapy.

EMS(8p11 myeloproliferative syndrome, EMS) is an aggressive hematological neoplasm with/without eosinophilia caused by a rearrangement of the FGFR1 gene at 8p11-12. It was found that all cases carry chromosome abnormalities at the molecular level, not only the previously reported chromosome translocation and insertion but also a chromosome inversion. These abnormalities produced 17 FGFR1 fusion genes, of which the most common partner genes are ZNF198 on 13q11-12 and BCR of 22q11.2. The clinical manifestations can develop into AML (acute myeloid leukemia), T-LBL (T-cell lymphoblastic lymphoma),

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… Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci U S A. (2005) 102(21):7665–70. doi: 10.1073/pnas.0502860102 107. Weinstein IB, Joe AK. Mechanisms of disease: Oncogene addiction–a rationale for molecular targeting in cancer therapy. …

Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls.

BackgroundThis study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications.MethodsDutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between 'all medic

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… L01XC15 | Obinutuzumab L01XC17 | Nivolumab L01XC18 | Pembrolizumab L01XC19 | Blinatumomab L01XC21 | Ramucirumab L01XC22 | Necitumumab L01XC23 | Elotuzumab L01XC24 | Daratumumab L01XC26 | Inotuzumab Ozogamicine L01XC27 | Olaratumab L01XC32 | Azetolizumab L01XD05 | Temoporfine L01XE01 | Imatinib L01XE02 | Gefitinib …

Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.

BackgroundThe overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for t

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… Phase i dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors. Cancer Chemother Pharmacol. 2014;74(6):1191–8. doi: 10.1007/s00280-014-2593-7. 36. …

Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.

The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation of the Shh pathway has been shown in a variety of human cancers, including, basal cell carcinoma, malignant gliomas, medulloblastoma, leukemias, and cancers of the breast, lung, pancreas, and prostate. Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and glioma-associated oncogene homolog (GLI) family of zinc

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… Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells Mol. Cancer Ther. 2010 9 617 630 10.1158/1535-7163.MCT-09-1013 20179163 PMC3228252 76. Fan Q. Gu D. He M. Liu H. Sheng T. Xie G. …

Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research.

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome e

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… Successful Rechallenge with Erlotinib in a Patient with EGFR-Mutant Lung Adenocarcinoma Who Developed Gefitinib-Related Interstitial Lung Disease. Cancer Chemother. Pharmacol. 2010;65:803–806. doi: 10.1007/s00280-009-1212-5. 61. …

New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors.

Bone tumors are tumors that occur in the bone or its accessory tissues, including primary tumors and metastatic tumors. The main mechanism of bisphosphonate is to inhibit the resorption of destructive bone, inhibit the activity of osteoclasts and reduce the concentration of blood calcium. Therefore, bisphosphonates can be used for malignant hypercalcaemia, pain caused by osteolytic bone metastasis, prevention of osteolytic bone metastasis, multiple myeloma osteopathy, improving radiosensitivity and so on. However, the traditional administration of bisphosphonates can cause a series of adverse

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… In future studies, chemotherapy drugs for lung cancer, such as gemcitabine, pemetrexed and vinorelbine, and tyrosine kinase inhibitors, such as gefitinib and axitinib, can be considered. …

Aptamer Therapeutics in Cancer: Current and Future.

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesize

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… For example, gefitinib (Iressa ® , AstraZeneca, Chesire, UK), the TKI for EGFR, binds with wild-type EGFR kinase at a Kd of 53.5 nM [ 5 ], while the Kd of cetuximab (Erbitux ® , ImClone, Branchburg, NJ, USA), an inhibitory anti-EGFR antibody, is far smaller, 2.3 nM [ 6 ]. …

Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are