Clinical and Translational Medicine, Год журнала: 2024, Номер 14(12)
Опубликована: Ноя. 26, 2024
Cancer remains the second leading cause of death globally, following cardiovascular disease, and represents a major public health challenge.1 It arises from extensive DNA damage induced by ultraviolet radiation, ionizing environmental factors, therapeutic agents. Among cancer types, most frequently diagnosed are lung (12.7%), breast (10.9%), colorectal (9.7%) gastric cancers (7.8%).2 In China, accounts for highest mortality, with 657 000 deaths (27.2%) crude mortality rate 47.5 per 100 individuals.3 According to World Health Organisation, contributes largest global disease burden, 244.6 million disability-adjusted life years (DALYs) lost, affecting both men (137.4 DALYs) women (107.1 DALYs).4 Consequently, there is an urgent need more effective medications strategies reduce minimize side effects, improve patient prognosis. While conventional anticancer treatments, such as surgery, radiotherapy hormonal therapy, have advanced, field therapeutics intensively focused on improving survival outcomes.5 Emerging therapies, including immunotherapy, gene molecular-targeted show particular promise in enhancing efficacy.5 these, therapy has gained attention its ability directly interfere oncogenic molecules, effectively blocking sites critical progression.6 Over past decade, antibody-drug conjugates (ADCs), which combine monoclonal antibody cytotoxic drug linked chemical bridge, achieved substantial success, due their highly selective delivery toxic agents cells.7 exploring diverse essential advancing development. Small-molecule drugs play role chemotherapy treating malignant metastatic diseases. 60% current originate natural sources, plants, animals microbes.8 For instance, vinblastine vincristine Catharanthus roseus (Apocynaceae), taxol docetaxel Taxus species (Taxaceae) camptothecin (CPT) Camptotheca acuminata (Nyssaceae) among chemotherapeutics available today.9 However, primary challenge developing nature-derived limited availability resources. Taxol, known high efficacy, low toxicity broad-spectrum activity, textbook case this challenge. To meet demand, large quantities trees been felled. This substantially contributed depletion these resources, since long developmental cycle. Currently, all 11 listed International Union Conservation Nature Red List Endangered Species 2013. Camptothecin monoterpene indole alkaloid that specifically targets topoisomerase I recognized third significant after vinblastine.10 With total trade volume exceeding $10 billion, CPT continues be focus development potent safer drugs. Modifications CPT's structure produced several derivatives, irinotecan, topotecan, belotecan, enhanced antitumor activity improved stability, introducing hydrophilic amino hydroxyl groups A/B rings CPT.11 Additionally, increasingly utilized payload ADCs small-molecule conjugates, optimizing potential.12 Because Nothapodytes contain 3–7 times than acuminata, genus become source 2003. nine species, primarily distributed across tropical regions southern southeastern Asia, overexploited. particular, over 80% plants Southwest China depleted, only small number now surviving protected areas (unpublished data). Thus, we urgently call conservation, protection sustainable use preserve valuable resources.1 Reproductive biology: Factors like flowering time, pollinator interactions seed dispersal mechanisms influence regeneration recovery potential plant populations under exploitation. Understanding how bioactive compound production impacts reproductive success conservation strategies.13 Spatio-temporal distribution: Studying spatial temporal distribution populations, along taxonomic clarification genetic diversity assessments, vital ensure efforts vulnerable populations. These studies lay foundation region-specific consider ecological pharmacological importance plants. Omics approaches: Genomic, population genomic, transcriptomic metabolomic approaches reveal metabolic diversity, enabling identification genes pathways involved synthesizing compounds.14, 15 Defence detoxification dynamics: Plants produce secondary metabolites defend themselves against biotic abiotic stressors, while herbivores pathogens evolve they can gut enzymes or microbes modify (toxins). Leveraging "defence detoxification" dynamics yield structurally molecules.16 Symbiosis: Symbiosis, particularly bacteria fungi, another avenue discovery. some cases, lateral transfer led symbiotic organisms acquire genes, them similar metabolites. example, fungi Aspergillus, Trichoderma, Fomitopsis, Phomopsis Fusarium found CPT.15 Synthetic modifications: Isolated products serve models analogues prodrugs. methodologies, combinatorial synthesis, crucial creating molecules effects. Advanced synthetic Function-Oriented Synthesis,17 Biology-Oriented Synthesis,18 Diversity-Oriented Synthesis19 Pharmacophore-Oriented SemiSynthesis20 should prioritized future research. conclusion, conserving threatened medicinal broad requires multifaceted approach. We prioritize resources within target taxa, encompassing biogeography, systematics, distribution. Equally important understanding accumulation active compounds scales, alongside photosynthetic physiological influences production. assessing pressures, endophytic may contribute essential. Investigating biosynthesis compounds, well pharmacokinetics pharmacodynamics, will further support efforts. Moreover, policy standards must established protect evaluating status resource supply. Strengthening pharmaceutical pipeline, ingredients, lead medicines, integrating advances pharmacology (Figure 1). Conceptulization: Gao Chen, Xianghai Cai, Jia Tang, Ge. Formal analysis investigation: Xingrong Peng. Writing—original draft preparation: Supervision: Chen. work was supported Key Project Basic Research Yunnan Province, (202301AS070001) Chen Revitalization Talent Support Program "Young Talent" (XDYC-QNRC-2022-0480) thank Guillaume Chomicki his help English Language. All authors discussion interpretation results. The declare no conflict interest.
Язык: Английский
