Creutzfeldt–Jakob disease (CJD) is a rare and still fatal neurodegenerative disorder caused by prion protein misfolding in the central nervous system. Accumulation of the pathogenic isoform leads to neuronal damage, spongiform degeneration, and rapidly progressive dementia. The disease is divided into sporadic, familial, iatrogenic, and variant forms, with sporadic cases accounting for the majority of cases. Diagnosis remains challenging and relies on a combination of clinical assessment, neuroimaging, and laboratory biomarkers. Key diagnostic methods include electroencephalography, Magnetic Resonance Imaging, and cerebrospinal fluid analysis for proteins as well as advanced amplification tests that improve diagnostic accuracy. Despite these advances, early detection remains challenging and misdiagnosis can occur. Currently, there is no effective disease-modifying therapy, and treatment is primarily supportive, focusing on symptom control and palliative care. Ongoing research aims to better understand the molecular mechanisms underlying prion propagation and develop targeted therapeutic strategies. This review summarizes current diagnostic methods and therapeutic approaches, focusing on molecular applications and their potential clinical implications.

Cetuximab and panitumumab are anti-EGFR monoclonal antibodies widely used for the treatment of colorectal cancers. However, due to various mechanisms of resistance to these targeted therapies, the patients’ responses vary. These resistances remain a major obstacle in treatment and overcoming them has become a key emphasis of current therapeutic strategies. Intrinsic and acquired resistance often lead to reactivation of downstream signaling pathways, mainly the RAS-RAF-MEK-ERK (MAPK pathway) and PI3K-AKT axes. Prior existing mutations in KRAS, NRAS, and BRAF result in primary resistance by constantly activating the signals, irrespective of EGFR inhibition. That said, acquired resistance manifests under therapeutic burden through the process of clonal evolution via KRAS and BRAF alterations, restoring MAPK pathway activity despite EGFR inhibition. In addition to those mutations, tumor cells exploit mechanisms independent of EGFR, such as the pathway bypass, which includes amplification of ERBB family receptors like HER2 (ERBB2) and activation of MET signaling. To overcome these resistances, novel strategies have emerged, which target multiple nodes within the oncogenic networks. Such methods include vertical pathway inhibition, multi-kinase inhibition, liquid-biopsy-guided therapy, and anti-EGFR rechallenge. Reactivation driven by secondary mutation can be prevented by targeting multiple nodes within the MAPK cascade simultaneously, which is referred to as the vertical pathway inhibition. Overall, this review underscores that overcoming therapeutic resistance requires a multidimensional approach that integrates molecular profiling, rational combination therapies, and adaptive treatment. Finally, these advances underscore the shift toward precision oncology, where therapy is tailored to tumor evolution, leading to improved response and patient outcome.

Porphyrins and their derivatives represent one of the most adaptable classes of compounds in contemporary biomedical research, bridging the crucial gap between diagnostic imaging and therapeutic intervention. This comprehensive review examines the evolution of porphyrin-based compounds and their therapeutic applications, from their fundamental role in photodynamic therapy to their status as sophisticated theranostic platforms. The unique photophysical properties of porphyrins, which are characterized by intense Soret band absorption, tunable fluorescence emission, and the generation of reactive oxygen species upon light activation, underpin their dual functionality as both imaging and therapeutic agents. The structural basis of porphyrin photochemistry, their progression through the first, second, and third generation of photosensitizers, and the transformative impact of nanotechnology, especially in overcoming intrinsic limitations such as poor aqueous solubility, aggregation-caused quenching, as well as limited tumor specificity, are discussed. Attention is devoted to emerging nanoplatforms such as porphyrin-based metal–organic frameworks (MOFs), covalent–organic frameworks (COFs), and electrospun nanofibers, which enable multimodal imaging, synergistic therapies, and controlled drug delivery. The challenges that impede clinical translation, including phototoxicity, tissue penetration limitations, and biosafety concerns, are critically examined, along with promising strategies for their resolution. By integrating porphyrin-based theranostic capabilities within single molecular platforms, these systems are ready to advance personalized cancer medicine while enabling real-time treatment monitoring and precision-guided interventions, which could substantially improve patient outcomes.