J Hematol Oncol
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B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as well as BCMA-targeted immunotherapeutic agents in different stages of clinical development.
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Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1), programmed cell death ligand-1 (PD-L1), and others have shown potent clinical efficacy and have revolutionized the treatment protocols of a broad spectrum of tumor types, especially non-small-cell lung cancer (NSCLC). Despite the substantial optimism of treatment with PD-1/PD-L1 inhibitors, there is still a large proportion of patients with advanced NSCLC who are resistant to the inhibitors. Preclinical and clinical trials have demonstrated that radiotherapy can induce a systemic antitumor immune response and have a great potential to sensitize refractory "cold" tumors to immunotherapy. ⋯ Notably, research has revealed that SBRT is superior to conventional radiotherapy, possibly because of its more powerful immune activation effects. Thus, PD-1/PD-L1 inhibitors combined with SBRT instead of conventional radiotherapy might be more promising to fight against NSCLC, further achieving more favorable survival outcomes. In this review, we focus on the underlying mechanisms and recent advances of SBRT combined with PD-1/PD-L1 inhibitors with an emphasis on some future challenges and directions that warrant further investigation.
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Ovarian cancer is one of the most lethal gynecologic malignancies reported throughout the world. The initial, standard-of-care, adjuvant chemotherapy in epithelial ovarian cancer is usually a platinum drug, such as cisplatin or carboplatin, combined with a taxane. However, despite surgical removal of the tumor and initial high response rates to first-line chemotherapy, around 80% of women will develop cancer recurrence. ⋯ Recent reports suggest that cells with impaired homologous recombination (HR) activities due to mutations in TP53 gene or specific DNA repair proteins are specifically sensitive to ataxia telangiectasia and Rad3-related protein (ATR) inhibitors. Replication stress activates DNA repair checkpoint proteins (ATR, CHK1), which prevent further DNA damage. This review describes the use of DNA repair checkpoint inhibitors as single agents and strategies combining these inhibitors with DNA-damaging compounds for ovarian cancer therapy, as well as the new platforms used for optimizing ovarian cancer therapy.
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Cancer heterogeneity is regarded as the main reason for the failure of conventional cancer therapy. The ability to reconstruct intra- and interpatient heterogeneity in cancer models is crucial for understanding cancer biology as well as for developing personalized anti-cancer therapy. Cancer organoids represent an emerging approach for creating patient-derived in vitro cancer models that closely recapitulate the pathophysiological features of natural tumorigenesis and metastasis. ⋯ Further, the synergistic combination of cancer organoids with organ-on-a-chip and 3D bioprinting presents a new avenue in the development of more sophisticated and optimized model systems to recapitulate complex cancer-stroma or multiorgan metastasis. Here, we summarize the recent advances in cancer organoids from a perspective of the in vitro emulation of natural cancer evolution and the applications in personalized cancer theranostics. We also discuss the challenges and trends in reconstructing more comprehensive cancer models for basic and clinical cancer research.
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N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. ⋯ Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.