Managing adverse events is important for optimizing cancer treatment and ensuring high patient satisfaction. Studies have assessed (1) anti-epidermal growth factor receptor (EGFR) monoclonal antibody-induced skin toxicities, (2) development of severe neutropenia by renally excreted anticancer drugs in patients with renal impairment (RI), and (3) pharmaceutical care in the treatment of immune checkpoint inhibitors (ICIs). We identified liver metastasis as a risk factor and preemptive systemic antibiotic administration with anti-inflammatory effect as a preventive factor for grade ≥2 overall skin toxicities in anti-EGFR treatment for metastatic colorectal cancer (mCRC). Additional prophylactic topical steroids to systemic minocycline significantly prevented grade ≥2 rashes, but did not mitigate overall skin toxicities. Patients receiving trifluridine/tipiracil (FTD/TPI)-based chemotherapy for mCRC were assessed, resulting in significantly higher early severe neutropenia development among patients with RI. Additionally, we assessed the impact of RI on severe neutropenia development in carboplatin+pemetrexed-based chemotherapy for thoracic cancer. Consequently, severe neutropenia in the first cycle and all-treatment cycles was significantly more confirmed in patients with RI. We assessed the usefulness of pharmaceutical interventions in ICI treatment, which suggested that pharmaceutical care may improve quality of outpatient ICI treatment, and pharmaceutical intervention during the first three months after initiation of ICI treatment is crucial. Our studies have found clinically important outcomes that support the provision of less onerous chemotherapy.

The field of epitranscriptomics, an area of genetics concerning the regulation of gene expression via post-transcriptional RNA modification, is currently attracting substantial research attention. In epitranscriptomics, proteins, collectively termed writers, erasers, and readers, enter into complex interactions that contribute to modifying RNA, thereby maintaining biological homeostasis. However, abnormalities in the expression or function of these proteins can lead to the onset and progression of cancers and neuropsychiatric disorders. Using prostate cancer clinical specimens, I cloned a novel gene, prostate cancer antigen-1 (PCA-1), containing a domain similar to the 2-oxoglutarate, iron(II) [Fe(II)]-dependent oxygenase domain of the Escherichia coli AlkB protein and characterized by enzymatic activity associated with the demethylation of methylated RNA. This was accordingly designated AlkB homolog 3 (ALKBH3). I demonstrate that ALKBH3 is highly expressed in tumor cells in prostate, pancreatic, lung, and other cancers, and its activity is correlated with a poor prognosis. In addition, I developed novel compounds that inhibit the RNA demethylase activity of ALKBH3, thereby providing a basis for developing a first-in-class cancer therapeutic. I also succeeded in cloning the ALKBH8 gene. High ALKBH8 expression was also observed in bladder cancer cells. Furthermore, abnormalities in development and behavior were noted in the generated Alkbh8 knockout mice. On the basis of the experience gained from ALKBH3 drug discovery research, I have established a foundation system for supporting academic drug discovery research. In this review, I describe the pathway followed in integrating the findings of basic pharmaceutical and drug discovery research and further developments.

The blood–retinal barrier (BRB) consists of the inner and outer blood–retinal barrier (abbreviated as inner BRB and outer BRB). The inner and outer BRB’s together regulate the transport of substances between the blood and neural retina via various membrane transporters. To utilize the oral administration for the pharmacotherapy of retinal diseases, it is necessary and important to understand many drug transport mechanisms in the BRB’s. This review discusses the BRB transport research reported over more than a quarter of a century, particularly the development of in vitro and in vivo transport evaluation systems as well as newly discovered BRB-specific cationic drug transport mechanisms.

Antibodies are endogenous proteins that are involved in humoral immunity. Although various therapeutic monoclonal antibodies (mAbs) targeting cancer and immune diseases have been widely used, the development of mAbs for the treatment of infectious diseases has remained limited. During the coronavirus disease 2019 (COVID-19) pandemic, various mAbs targeting the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed, received Emergency Use Authorization (EUA), and were used for treating and preventing COVID-19. As successive SARS-CoV-2 variants emerged and the pandemic spread, mAbs with high target specificity proved less effective against these variants. Consequently, their EUAs were suspended within a short period, highlighting the limitations of antiviral mAbs developed against emerging infectious diseases. Since 2021, guidance documents on mAbs for prevention and treatment of COVID-19 have been issued by the WHO and US FDA, and efforts to prepare a regulatory environment supportive of drug development for future emerging and re-emerging infectious diseases have accelerated. The EMA published a concept paper on development of guidelines for non-clinical and clinical evaluation of mAbs for COVID-19. These trends indicate that the international regulatory landscape for mAbs against infectious diseases is entering a new era. We here provide an overview of the guidance documents issued by regulatory agencies, based on insights obtained from anti-SARS-CoV-2 mAbs during the COVID-19 pandemic. We also discuss the challenges and future prospects for the development of mAbs against infectious diseases, particularly in situations requiring rapid responses during pandemics.

The interactions between 4 compounds used as influenza neuraminidase inhibitors—oseltamivir, zanamivir, laninamivir, and peramivir— and influenza virus neuraminidase were analyzed using pair interaction energy decomposition analysis based on fragment molecular orbital (FMO) method, quantitatively elucidating binding characteristics of each inhibitor. Our calculations revealed that structures with common functional groups showed similar binding characteristics, whereas structures with functional groups differing in hydrophilicity/hydrophobicity showed different types of intermolecular interactions for the same amino acid residues. Such analysis is expected to be effective for precise molecular design in structure-based drug design.

Patients diagnosed with metastatic or recurrent cancer experience uncertainty and distress; however, their consultation needs remain insufficiently quantified. We conducted a web survey in Japan (January 23–29, 2025) among adults (≥18 years) with a history of metastatic or recurrent cancer (n=522). Participants selected concerns from 21 items across four domains, and for each endorsed concern, they indicated whether they wished to consult hospital and/or community pharmacists; consultation intention was calculated among those endorsing each item. Hospital–community differences were evaluated using McNemar’s test or Mid-P exact test using a significance threshold of p<0.001. The mean age was 58.9±12.9 years; cancers were colorectal (22.2%), breast (18.2%), lung (11.9%), and gastric (11.1%). 88.7% reported at least one concern. The most common concerns were treatment-related side effects (51.0%), anticancer drug mechanism/efficacy (46.9%), treatment costs (42.1%), mental distress (35.1%), and medications used to alleviate cancer- or treatment-related physical discomfort (34.7%). Consultation intention was higher for hospital than community pharmacists for issues including side effects (43.2 vs. 16.2%), mechanism/efficacy (42.9 vs. 18.0%), and symptom-relief medications (48.6 vs. 24.9%). Although concerns regarding medications other than cancer treatment were uncommon (<10% each), consultation intention exceeded 40% when present. These findings indicate that patients with metastatic or recurrent cancer may perceive different consultation roles for hospital and community pharmacists, particularly according to the type of concern. Because these results are based on self-reported consultation intentions rather than actual consultation behavior, they should be regarded as hypothesis-generating and as a basis for future studies on coordinated pharmacist support.