Molecular Oncology Research Highlights 2023

Looking back at the exciting developments across all fields of cancer research and policy we had the pleasure of sharing with you in 2023, we selected several papers which we feel represent interesting concepts and directions that may shape future cancer research
Molecular Oncology Research Highlights 2023
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The progress in effectively treating patients with cancer relies on discoveries in basic and translational research that when tested in clinical trials leads to favourable outcomes in cancer diagnostics, treatment and care. Equal access to cancer diagnostics, treatment and care is key for people to reap the benefits of basic research and the efforts, resources and time put into such studies. The Meeting report by Ringborg, Heitor, Berns et al outlined recent discussions on how infrastructures can be effectively shaped to better achieve translational, prevention, clinical and outcomes cancer research, with a focus on sustainability while engaging patients and the public. For cancer research progress to accelerate, it is important that key findings are reproducible and can be replicated or used by other researchers. Attention to this matter is brought by the Viewpoint by Untergasser, Hellemans, Pfaffl et al proposing a set of recommendations aimed at increasing accurate documentation of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) procedures and sharing of raw data for reported experiments.

 

 From cancer biology basics to fueling drug development

 Innovation in cancer therapy trends stems from a better understanding of the basic principles underlying cancer biology. In this review Lucia Robado de Lope et al, invited readers to approach cancer as an infective disease in order to provide insights into the role of extracellular vesicles (EVs) in tumourigenesis. Not long after its addition to the collection of possible RNA modifications, the role of N6‐methyladenosine (m6A) in cancer aetiology is under heavy investigation. In their review Wang et al focused on the functions of this dynamic modification in cancer development, also highlighting its potential as a biomarker for cancer diagnosis.

 In addition, researchers have taken diverse approaches to bring new targets governing cancer signaling to the spotlight potentially highlighting their use in cancer treatment development, as seen by publications in Molecular Oncology over the last year:

  

  • Candiello et al used transcriptomic analyses to show that miRNA-483-3p directly targets NDRG1 and suppresses its expression in metastatic colorectal cancer, upregulating the EGFR/ERBB3 signaling pathway.
  • Babačić et al identified non-canonical peptides from glioblastoma cancer stem cell and proposed a proteomic signature characterizing two distinct phenotypic conditions with inverse associations with clinical outcomes.
  • Petersen et al used proximity-dependent labeling with biotin followed by mass spectrometry to reveal the interactome of ABI1 and a previously unrecognised role in TAK1/RIPK1-based regulation of cell death.
  • Whyte et al cautioned that inhibition of NUAK1 as a therapeutic approach against pancreatic ductal adenocarcinoma (PDAC) may be accompanied with genotoxic stress due to a role in centrosome replication.
  • Lopez-Mejia et al employed a peptide-based tyrosine-kinase-activity profiling approach to quantify changes in tyrosine kinase activation between uterine serous carcinoma and endometrioid endometrial carcinoma and identified FAK to be highly activated by ROS in the former.
  • Kumar et al predicted the association of immunoproteasome expression with overall survival and response to immune checkpoint blockade therapy is tumour-type specific (better in some cancer types but worse in others) and is greatly influenced by pro- or anti-tumourigenic immune cell infiltration patterns. 
  • Wu et al performed parallel genomic comparisons between matched brain metastasis and primary tumor DNA, plasma circulating tumour DNA (ctDNA) and cerebrospinal fluid (CSF) ctDNA, highlighting CSF ctDNA could detect all brain metastasis mutations in 83% of patients vs 27.78% with plasma ctDNA

 

 Overcoming hurdles in the race to efficacious cancer treatment

 Several oncogenic factors have been in the spotlight as a research focus recently. A common obstacle preventing the translation of useful therapies targeting such factors to the clinic has been therapy resistance. For instance, resistance to ALK inhibitors in non-small cell lung cancer may arise due to point-mutations in subunits of a EML4-ALK fusion protein, as discussed by Elshatlawy et al in a Review on the biology of EML4-ALK variants and ALK-TKI drug resistance mechanisms.

 Strategies to improve sensitivity to existing therapeutic modalities or the creation of novel treatment regimes combining existing drugs have been met with various degrees of success:

 

  • Antonio Mulero-Sánchez et al showed that co-inhibition of both mTOR and SHP2 is highly synergistic in vitroby triggering apoptosis in hepatocellular carcinoma.
  • Blasquez et al described ebselen oxide could antagonise overexpressed HER2, as well as mutated and truncated oncogenic forms of HER2, blocking HER2+breast tumor progression in vivo
  • Haselager et al demonstrated how NF-κB inducing kinase (NIK) inhibition interrupted the NF-κB/STAT crosstalk and resensitized chronic lymphocytic leukaemiacells to venetoclax.
  • While studying tetraploid cells, Yoshizawa et al documented that these cells are more susceptible to inhibitors of mitotic kinesin (CENP-E) than diploid cells and CENP-E inhibition was more potent across a broader spectrum of cell lines compared to paclitaxel in its tetraploidy selectivity.

 

Lessons learned from treating cancer patients

 A comprehensive follow-up of patients treated in the clinics can better inform us about the genomic landscape post-therapy, as well as instruct cancer diagnostics technologies via stratifying cancer biomarkers and other predictors of treatment efficacy. Identifying common patterns of mutations and biomarkers may aid in patient stratification and improve therapy efficacy across various patient cohorts.

 

  • Chen et al explored the impact of genomic (co-)alterations on clinical outcomes with one of the largest clinico-genomic datasets of ER+, HER2−, PIK3CAmut breast cancer patients treated with taselisib + fulvestrant.
  • Carbonell et al implemented shallow WGS on plasma cell-free DNA from 45 patients with metastatic NSCLC treated with immune checkpoint inhibitors to monitor how tumor fraction and somatic copy number alteration burden correlates with treatment benefit and clinical features.
  • Amrutkar et al carried out comparative proteomic profiling of tumor tissue samples from treatment-naïve and neoadjuvant chemotherapy-treated PDACs and found significantly lower expression of metabolic proteins in treated tumours.
  • Maansson et al undertook H3K36me3 cell-free DNA ChIP followed by targeted NGS on blood plasma samples from lung cancer patients and controls demonstrating increased enrichment of mutated alleles vs normal alleles in plasma from patients with known somatic cancer mutations. 

 

 You may also access our collection of highlighted articles here:

https://febs.onlinelibrary.wiley.com/doi/toc/10.1002/(ISSN)1878-0261.2023-highlights

  

Would your own research fit well within this collection? Then we encourage you to submit your manuscript to our journal.

Cover image from © Piroshki-Photography via Canva.com

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