Targeted therapies

Overview

Targeted therapies represent a class of precision medicine interventions designed to interfere with specific molecular targets—proteins, genes, or signaling pathways—that are causally implicated in the growth, progression, and survival of disease. Unlike conventional cytotoxic chemotherapy, which broadly disrupts rapidly dividing cells, targeted therapies act on molecularly defined vulnerabilities, such as oncogenic driver mutations, dysregulated kinases, or aberrant signaling cascades including the PI3K/Akt signaling pathway and MAPK networks. This specificity allows for greater therapeutic selectivity and, in many cases, improved tolerability compared to traditional systemic treatments.

The biological rationale for targeted therapy rests on the concept of oncogene addiction and molecular dependency: tumor cells harboring activating mutations in genes such as BRAF, KRAS, or transcription factor networks driven by proteins like MYCN become disproportionately reliant on those pathways for survival, rendering them acutely sensitive to pathway inhibition. Beyond oncology, targeted therapies are increasingly relevant in inflammatory diseases, infectious conditions, and metabolic disorders, wherever discrete molecular mechanisms can be pharmacologically exploited. The expanding integration of genomics, proteomics, and multiomics has accelerated the identification of actionable targets, positioning targeted therapies at the center of modern translational medicine.

Focus of Latest Publications

Recent literature demonstrates that targeted therapies occupy a central and expanding role across a broad spectrum of disease contexts, with research efforts focused on identifying new molecular targets, overcoming resistance, improving patient stratification, and navigating barriers to clinical access.

Oncology: Solid Tumors and Hematologic Malignancies

In lung cancer, targeted therapies—alongside immunotherapy—have been credited with revolutionizing treatment paradigms and extending patient survival, with a current research roadmap emphasizing continued advances in early detection, therapeutic innovation, and prevention (PMID: 42001483). Similarly, in the management of stage III resectable melanoma, both immunotherapy (IO) and targeted therapies have been formally recommended as adjuvant treatment options, reflecting a shift toward precision-based post-surgical care (PMID: 42260049).

BRAF-altered glioma represents a paradigmatic case where genomic characterization has directly enabled targeted intervention. Consensus guidance from the Society for Neuro-Oncology (SNO) and the European Society for Neuro-Oncology (EANO) underscores that patients with BRAF alterations may receive targeted treatments in addition to standard glioma therapies, supported by evidence spanning randomized trials, single-arm studies, and real-world data (PMID: 42261252). This illustrates the increasingly individualized nature of neuro-oncological care.

In pancreatic cancer—a disease long recalcitrant to systemic treatment—studies on phenylcarbamic acid inhibitors (PCAIs), tested in MIA PaCa-2 and PANC-1 cell lines harboring KRAS mutations, demonstrated the capacity of these agents to inhibit metastasis and tumor growth via hyperactivation of the MAPK and PI3K/AKT pathways, positioning them as candidate targeted therapies for KRAS-driven malignancies (PMID: 42233520). Given the critical oncogenic role of KRAS across multiple cancer types, these findings have broad translational implications.

Neuroblastoma research has focused on disrupting the MYCN interaction network—particularly its association with the partner protein Max—as a route to targeted therapies in MYCN-amplified disease (PMID: 42233780). Early-phase clinical trials assessing targeted therapies across oncology indications continue to display a wide range of efficacy and toxicity profiles, emphasizing the need for rigorous biomarker-driven patient selection (PMID: 42013511).

For medulloblastoma, integrated molecular profiling combining genomics and transcriptomics has refined subtype classification and informed the selection of targeted therapies, though the real-world clinical utility of such comprehensive profiling remains incompletely defined (PMID: 42056683). In metastatic renal cell carcinoma (mRCC), aberrant alternative splicing events are being characterized for their association with clinical benefit from both immune checkpoint inhibitors and targeted therapies, opening new avenues for patient stratification (PMID: 42086309).

In metastatic colorectal cancer, large-scale analyses of first-line chemotherapy administered with or without targeted therapies have explored sex differences in efficacy and toxicity across more than 18,000 patients in the ARCAD CRC database (PMID: 41903302), highlighting the importance of demographic variables in treatment optimization.

In chronic lymphocytic leukemia (CLL), the therapeutic landscape has undergone a fundamental shift from chemoimmunotherapy toward targeted therapies—including agents such as venetoclax—delivered either as continuous treatment until progression or in fixed-duration regimens, a transition with significant implications for patient quality of life and long-term disease management (PMID: 41627367).

In hepatocellular carcinoma (HCC), a systematic bibliometric analysis of natural compounds—including curcumin, quercetin, and resveratrol—over the 2015–2025 period has established a cataloging framework to prioritize molecules for future trials as potential novel targeted therapies (PMID: 42061133).

Non-Oncologic Applications

Beyond cancer, targeted therapies are increasingly relevant in dermatology. The growing use of biologics and other targeted agents in psoriasis and atopic dermatitis has revealed a treatment-associated "flip-flop" phenotype switch, wherein patients treated for one condition develop features of the other, underscoring the shared and divergent immunological pathways—involving regulatory T cells and growth factors such as TGF-β1 and VEGF—that these therapies engage (PMID: 42132049).

In infectious disease, nanotechnology-based approaches using Cu-Mn nanoparticles functionalized with PEGylated chitosan have demonstrated targeted treatment potential against methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia in preclinical models, reflecting the extension of targeting principles beyond molecular oncology into antimicrobial therapy (PMID: 42024082).

For diabetic complications, large-scale proteomics analyses are being used to identify biomarkers that can guide targeted therapies in patients with hyperinsulinemic T2D and related metabolic disorders, with Aurora kinase A among proteins flagged as a potential molecular target (PMID: 42019187). Mastitis in dairy cattle has similarly been approached through bioinformatics-driven target identification, with a framework proposed for developing targeted therapies and diagnostic tools to improve herd health (PMID: 42127079).

Systemic and Translational Challenges

Across all disease domains, several cross-cutting challenges recur. The role of the gut microbiota in modulating drug response—including responses to targeted therapies—is an emerging area of investigation, with key challenges including proving causation, elucidating context-dependent mechanisms, and translating patient heterogeneity into robust biomarkers (PMID: 41963781). In critical care, pathway biology examining coordinated dysregulation of molecular networks—rather than isolated analytes—is proposed as the conceptual anchor for matching patients to targeted therapies in trials (PMID: 42201983).

Exosome-mediated crosstalk between immune cells and the tumor microenvironment has been implicated in resistance to targeted treatment, chemotherapy, and immunotherapy in lung cancer, with exosomes modifying intracellular signaling, reshaping the microenvironment, and transferring resistance-conferring proteins (PMID: 41759799). macrophage polarization and oxidative stress within the tumor microenvironment are additional modulators of targeted therapy response that continue to be actively investigated.

Finally, structural and policy barriers significantly affect access to targeted therapies for early-stage cancers. Despite clinical advances, reimbursement challenges and access inequities persist (PMID: 41653456), while the evaluation of targeted oncology medicines in health technology assessment frameworks is complicated by reliance on single-arm trials, tumor-agnostic indications, and novel endpoints that do not fit traditional evidence models (PMID: 42089946).

Key Publications

• Jun Epidemiology and Treatment Patterns of Stage III Resectable Melanoma Treated with Adjuvant Therapy: A Real-World Study Using the SNDS Database in France. (Dermatology and therapy, 2026, PMID 42260049): "IO and targeted therapies were recommended as adjuvant therapies for the treatment of stage III resectable melanoma."
• Jun BRAF-altered glioma in adults and children: A Society for Neuro-Oncology (SNO) and European Society for Neuro-Oncology (EANO) consensus review on clinical management and future directions. (Neuro-oncology, 2026, PMID 42261252): "In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence."
• Jun The anticancer effects of PCAIs in pancreatic cancer cells involve MAPK and PI3K/AKT pathways hyperactivation. (Oncotarget, 2026, PMID 42233520): "Taken together, these data obtained using pancreatic cancer cells with KRAS mutations suggest the ability of the PCAIs to prevent metastasis and tumor growth, strongly indicating their potential to serve as effective targeted therapies for treating cancer types driven by the multiple mutant forms of KRAS."
• Jun Targeting the MYCN interaction network in neuroblastoma. (Bioscience reports, 2026, PMID 42233780): "these approaches provide promising routes towards targeted therapies for MYCN-driven neuroblastoma."
• Jun Evolving landscape of targeted therapies in early phase clinical trials. (European journal of cancer (Oxford, England : 1990), 2026, PMID 42013511): "Early phase clinical trials assessing targeted therapies have historically been associated with a wide range of efficacy rates and toxicities."
• Jun Unveiling novel biomarkers for diabetes-related complications through large-scale proteomics analysis: A FIELD sub-study. (Journal of diabetes and its complications, 2026, PMID 42019187): "Identifying robust biomarkers is critical for improving risk prediction, understanding disease mechanisms, and guiding targeted therapies."
• Jun The Tip of the Iceberg: Pathway Biology Must Anchor the Next Generation of Critical Care Trials. (Critical care explorations, 2026, PMID 42201983): "Pathway biology, examining coordinated dysregulation of molecular networks rather than isolated analytes, offers the deeper resolution needed to match patients to targeted therapies."
• Jun Phytochemical frontiers and molecular targets in liver cancer: A systematic bibliometric curation of natural compounds for HCC therapy (2015-2025). (Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2026, PMID 42061133): "The systematic cataloging of authors, institutions, publishers, journals, and phytochemicals offers a foundation for prioritizing molecules in future trials, providing objective insights for drug discovery and potential novel targeted therapies for HCC."
• May Treatment-associated phenotype switching between psoriasis and atopic dermatitis. (Journal of the European Academy of Dermatology and Venereology : JEADV, 2026, PMID 42132049): "Increasing use of targeted therapies has revealed a treatment-associated phenotype switch between these conditions, the so-called 'flip-flop' phenomenon, characterized by sustained emergence of eczematous features in patients treated for psoriasis or psoriasiform disease in those treated for AD."
• May Bioinformatics approach to identify potential biomarker and drug target for the clinical and subclinical mastitis disease in dairy cattle. (PloS one, 2026, PMID 42127079): "This integrative approach not only provides insights into the molecular mechanisms underlying mastitis but also offers a robust framework for developing targeted therapies and diagnostic tools, ultimately contributing to better herd health and productivity."