This journal comprises ten sections, each of which consists of Specialty Chief Editors, Associate Editors, Review Editors and Guest Associate Editors. Applications for Associate or Review Editors and proposals for Research Topics are welcome.

“Molecular Medicine and Cancer Treatment”, “Molecular Medicine for Cardiology”, “Molecular Microbes and Disease”, and “Molecular Mechanisms of Neurodegeneration” are disease-oriented sections that address human diseases, such as cancers, cardiovascular diseases, infectious diseases, and neurological diseases. Other common or rare diseases are also within the scope of our journal. Please consult editorial staff about the section to submit. A proposal of disease-oriented Section other than those mentioned above will be considered positively from viewpoints of innovativeness and networking potential of the applicant for its Specialty Chief Editor.

In contrast, “Bioinformatics and Artificial Intelligence”, “Cell Therapy”, “Gene and Viro-therapy”, “Molecular Mechanisms of Immune Response”, “Molecular Pathology”, and “Single Cell Analysis” are methodology-oriented Sections that address cutting-edge technologies, including antibody-drug conjugates (ADCs), bispecific antibodies, chimeric antigen receptor-modified T (CAR-T) cells, clinical bioinformatics, clinical sequencing, complete-genome sequencing, digital pathology, explainable artificial intelligence, liquid biopsy, oncolytic viruses, pluripotent stem cells, protein degraders, single-cell analyses, spatial biology, and telemedicine.

Cross-boundary interactions among disease- and methodology-oriented sections during the editorial process of submitted manuscripts as well as through arrangements of joint Research Topics are critical features of our journal for driving knowledge generation and horizontal innovation in the field of molecular medicine (Figure 1).

SARS-CoV-2 enters and infects host cells through angiotensin converting enzyme 2 (ACE2) on endothelial cells, enterocytes and type II pneumocytes (Ziegler et al., 2020) as well as neuropilin-1 (NRP1) on endothelial cells, lung epithelium and olfactory epithelium (Cantuti-Castelvetri et al., 2020). COVID-19 patients present with fever, cough, fatigue, headache, hyposmia, hypogeusia, diarrhea and other symptoms, and some patients progress to severe conditions owing to respiratory, cardiovascular or cerebrovascular complications (Chen et al., 2020; Ellul et al., 2020; Nishiga et al., 2020). The case fatality rate of the general population with COVID-19 infection in the Worldmeters database is approximately 2.1% (3,331,763 of 160, 339, 530, as of May 12, 2021) (Worldometer, 2021); however, the rates of hospitalized COVID-19 patients in subgroups, such as the elderly, males, patients with diabetes, and the patients with hypertension and cardiovascular disease are much higher (Zhou F. et al., 2020; Grasselli et al., 2020).

Vaccines (BNT162b2, mRNA-1273, NVX-CoV2373, AZD1222 and Ad26.COV2.S) and therapeutic antibody cocktails (REGN-COV2) are SARS-CoV-2-targeted drugs for preventing infection or aggravation of COVID-19 (Polack et al., 2020; Ramasamy et al., 2020; Baden et al., 2021; Sadoff et al., 2021; Shinde et al., 2021; Weinreich et al., 2021). SARS-CoV-2 N501Y variants (B.1.1.7 in the United Kingdom) spread rapidly owing to increased affinity to ACE2 receptor, whereas SARS-CoV-2 N501Y/E484K variants (B.1.351 in South Africa) prone to escape antibody-mediated neutralization (Collier et al., 2021; Zhu et al., 2021). BNT162b2 vaccine showed 89.5 and 75.0% efficacies against B.1.1.7 and B.1.351 variants (Abu-Raddad et al., 2021). Because neutralization antibodies and T cell immunity are anti-viral mechanisms of dual wielding vaccines, vaccine-elicited T cell immunity might explain the benefits of vaccination against B.1.351 variants. Vaccine-based elimination is an optimal strategy to contain SARS-CoV-2 worldwide; however, global surveillance of SARS-CoV-2 variations and cyclic vaccinations targeting escape mutants might be necessary.

Repurposed drugs, such as anti-interleukin six receptor monoclonal antibodies (tocilizumab), broad-spectrum antiviral drugs (remdesivir) and corticosteroids (dexamethasone), are being applied to treat or ameliorate the symptoms of COVID-19 patients (Goldman et al., 2020; Stone et al., 2020; Tomazini et al., 2020), while an investigational ATR inhibitor (berzosertib) for the treatment of cancer patients with ARID1A, ATM and SMARCA4 alterations based on synthetic lethal strategy (Williamson et al., 2016; Gupta et al., 2020; Yap et al., 2020) showed anti-SARS-CoV-2 activity in preclinical experiments (Garcia et al., 2021). Small-molecule compounds that block replication of SARS-CoV-2 would be game changers to end the COVID-19 pandemic in a few years.

In contrast, SARS-CoV-2 elicits versatile COVID-19 pathologies through direct infections, immunological responses and vascular damage in multiple organs or tissues. Because chronic persistent infection with hepatitis viruses and Helicobacter pylori cause liver cancer and gastric cancer, respectively (Ajani et al., 2017; McGlynn et al., 2021), and intracranial inflammation causes neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease (Heppner et al., 2015; Poewe et al., 2017), SARS-CoV-2 might also promote carcinogenesis or dementia through persistent chronic infection, dysregulated host immunity or vasculopathy. Epidemiological studies based on genomic analyses and mechanistic studies based on single-cell analyses should be conducted to elucidate the spatiotemporal profiles of COVID-19 pathologies in the future.

Whole-exome and whole-genome sequencing analyses on bulk tumors has revealed the genomic landscape of human cancers, including point mutations, fusions, gene amplifications and (super)enhancer alterations in cancer-related genes as well as numerous variants of unknown clinical significance (Rheinbay et al., 2017; Wong et al., 2020). Fusions of the BCR and ABL genes (BCR-ABL) in chronic myelogenous leukemia (Rosti et al., 2017), gain-of-function mutations of the epidermal growth factor receptor (EGFR) gene in lung cancer (Herbst et al., 2018), fusions of the fibroblast growth factor receptor 2 (FGFR2) gene with the BICC1, KIAA1598, MGEA5, PPHLN1 or TACC3 gene in cholangiocarcinoma (Katoh, 2019), amplifications of the HER2 (ERBB2) gene in breast cancer (Oh and Bang, 2020) and exon 14 skipping mutations of the MET gene in lung cancer (Paik et al., 2020) are representative cancer drivers that are targeted by small-molecule inhibitors or antibody-based biologics in the clinic; however, there remain many cancer drivers that have not yet been successfully targeted in clinical practice.

For example, WNT signals are transduced to canonical and non-canonical pathways (Katoh and Katoh, 2007), and the canonical WNT signaling cascade is aberrantly activated in cancer patients owing to loss-of-function alterations in the APC, AXIN1, AXIN2, RNF43 and ZNRF3 genes or gain-of-function alterations in the CTNNB1 gene encoding β-catenin (Clara et al., 2020; Jung and Park, 2020). Investigational WNT signaling blockers of diverse therapeutic modalities, such as small-molecule compounds, peptide mimetics, antibody-based drugs and CAR-T cells, have shown striking benefits in preclinical studies but have not yet been approved for the treatment of cancer patients. Because the canonical WNT signaling cascade is involved in tumorigenesis as well as gastrointestinal, osteogenic and neuronal homeostasis (Katoh and Katoh, 2017), the therapeutic range of WNT signaling blockers might be too narrow for clinical application. Oncodevelopment signaling pathways with versatile functions in adult tissue homeostasis are hard targets for anticancer drug development.

Tumor heterogeneities, classified into interspecies, interpatient and intrapatient heterogeneity, are other obstacles to therapeutic development. Interspecies heterogeneity between human tumors and engineered mouse models is caused by species divergence in the coding regions and noncoding regulatory regions (Cornelissen et al., 2019; Pembroke et al., 2021). Interpatient heterogeneity or diversity is not completely recapitulated in human cell lines, xenografts and organoids owing to relatively small sample size and biases during the establishment procedure (Pauli et al., 2017; Bleijs et al., 2019). Engineered mouse models and patient-derived cell lines, xenografts and organoids are valuable tools for the screening and optimization of investigational drugs in preclinical studies; however, interspecies heterogeneity and interpatient heterogeneity might lead to the development failure of investigational drugs. A deep understanding of interspecies and interpatient heterogeneities with the aid of artificial intelligence and human intelligence would improve the success rate of drug development through orchestration of preclinical studies depending on therapeutic targets and drug moieties.

Intrapatient heterogeneity, further subclassified into intratumor and intertumor heterogeneities, is a hallmark of real tumors. Because antitumor immunity and therapeutic insults damage cancer cells but promote intratumor heterogeneity through acquired genetic alterations (Katoh, 2017; Marusyk et al., 2020), intratumor heterogeneity induces tumor evolution and subsequent intertumor heterogeneity of primary and metastatic lesions (Katoh, 2019; Vitale et al., 2021). Diagnostic genome sequencing based on a panel of approximately 500 cancer-related genes has been applied in the clinic to identify targetable cancer drivers (Katoh and Katoh, 2020; Yu et al., 2021); however, after targeted therapies, cancer drivers and dominant clones could be substituted by others to elicit therapeutic resistance. Temporal monitoring of cancer drivers for the optimization of targeted therapy is mandatory to improve the benefits and response rates of genome-based medicine.

The tumor microenvironment consists of slow-cycling cancer stem cells, proliferating cancer cells and noncancerous cells, such as cancer-associated fibroblasts, endothelial cells, immune cells and neurons (Lambrechts et al., 2018; Altorki et al., 2019). Paracrine and juxtacrine signaling networks within the tumor microenvironment, such as the WNT, FGF and Notch signaling cascades, maintain slow-cycling cancer stem cells and regulate tumor plasticity through omics reprogramming (Katoh, 2017; Katoh and Katoh, 2020). Complete or whole genome sequencing and single-cell analyses should be practiced in preclinical studies to decipher components of and networking within the tumor microenvironment for drug target discovery. Targeting aberrant features of the tumor microenvironment, such as immune evasion, matrix remodeling, metabolic adaptation and tumor angiogenesis, is an alternative strategy for cancer therapy compared with direct targeting of oncogenic drivers in cancer cells themselves (Valkenburg et al., 2018; Sahai et al., 2020).