Year: 2024
Type: editorial
Abstract: Significant progress has been made regarding the treatment of many cancers, but challenges remain. One in two people will develop cancer, mostly in old age and the need is to move away from systemic cytotoxic therapies. Treatment of advanced and metastatic disease has not improved substantially for 40 years with many of these cancers viewed as untreatable.A key to unlocking new treatments for advanced cancers is the existence of cancer stem cells (CSCs). They sustain a cancer by producing a hierarchy of differentiated or poorly differentiated cells and seem to be responsible for aggressive and metastatic disease. CSCs are insensitive to chemotherapy and persist giving rise to disease relapse. Desmoplastic small round cell tumour (DSRCT), which is driven by EWSC1-WT1 fusion oncogene, is a rapidly progressing pediatric cancer that is not curative. Magrath and co-workers have examined the existence of CSCs within DSRCT and shown that expression of stemness markers (SOX2 and NANOG) relates to a worse patient survival and elevated expression for metastatic DSRCT.They modelled CSCs in vitro by establishing tumour spheres that have an increased level of stemness markers. Though resistant to doxorubicin, tumour spheres were sensitive to EWSC1-WT1 knockdown leading to the possibility of targeting to eradicate DSRCT CSCs.To what extent the behaviour of CSCs differs from that of normal stem cells is all important to killing CSCs and sparing normal stem cells. The sustained production of a hierarchy of leukaemia cells by leukaemia stem cells (LSC) is akin to generating various blood cells by haematopoietic stem cells (HSCs). In new models for haematopoiesis, HSCs choose a cell lineage directly from a spectrum of all end-cell options. Their developmental trajectories are progressive and broad whereby HSCs can still veer towards an adjacent option. Whilst many leukaemias are likely to arise from a HSC, they are categorised based on the cells belonging to a cell lineage. Chronic myeloid leukaemia (CML) arises from transformation of a HSC and, by contrast to the cell of origin, the progeny of CML LSCs is restricted largely to neutrophils. Brown examines the view that some leukaemia signature oncogenes guide and restrict the cell lineage upon transformation of a HSC/progenitor cell.Tongue squamous cell carcinoma is an aggressive and highly metastatic cancer. To find druggable targets for patients who are resistant to neoadjuvant therapy George and coworkers compared the proteomic and phospho-proteomic profiles for primary tumors from resistant and sensitive patients. These analyses revealed a signature for neoadjuvant resistance. MAPK1, AKT1, and MAPK3, enrichment of Rho GTPase signalling and hyperphosphorylation of proteins that are involved in cell mobility, invasion, and drug resistance were predictive of resistance. Differences in the phosphorylation of keratins (KRT10 and KRT1) were also observed.The cytokine VEGF-A is the most potent stimulant of angiogenesis and is a major therapeutic target for cancer because angiogenesis is important to tumour growth. The predominant isoform of VEGF-A is VEGF165, and its heparin-binding domain (HBD) plays a critical role in mitogenicity. Takada and colleagues have shown that integrin v3 binds to the isolated heparin-binding domain of VEGF165 and discovered that VEGF165 binds to VEGFR2/KDR domain 1 (D1, in addition to domains 2 and 3). They identified the VEGF165 HBD amino acids that are required for these interactions. A VEGF165 mutant that was defective in αvβ3 and KDR D1 was unable to induce the phosphorylation of ERK1/2 and integrin β3 or support endothelial proliferation. From other findings, Takada and colleagues have argued that integrin αvβ3 is a negative regulator of VEGF165 signalling which is supported by integrin αvβ3 knockout mice having VEGF165 enhanced signalling.Re and coworkers summarise advances regarding promising news drugs for the treatment of pediatric and adolescent patients with Hodgkin lymphoma. Current strategies have achieved a better balance between supporting survival versus the long-term toxicities. Even so,
Authors: Geoffrey Brown, Andrew Liss
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4401101647