To mark the World Cancer Research Day 2021, we are pleased to highlight a collection of articles on cancer research published recently in The FEBS Journal.

In her recent interview for The FEBS Journal (1), Christine Watson, Professor of Cell and Cancer Biology at the University of Cambridge, discusses her lab’s focus on the mechanisms underlying lineage commitment of mammary stem and progenitor cells and the regulation of cell death in involuting mammary gland. Importantly, Christine also comments on her studies that revealed the constitutive activation of STAT3 in breast cancer, a finding that showcased STAT3 as a major therapeutic target.

In this review by Fernanda Kugeratski and Raghu Kalluri (2), the authors summarise the current knowledge on exosome-mediated regulation of white blood cell types in cancer and discuss engineered exosomes as potential immunomodulatory agents for cancer therapy.

Maartje Damen, Jacco van Rheenen and Colinda Scheele (3) review the role that dormant cancer cells play in cancer recurrence and explore therapeutic strategies that can be recruited to target these cells.

Tumor-associated macrophages (TAMs) play essential roles in the modulation of the tumour microenvironment, affecting in this way the metastatic potential and aggressiveness of cancer cells. This is the topic of the review by Shijia Yan and Guohui Wan (4) which focuses on the various origins of TAMs, as well as on the ways in which they affect the oncogenic potential of cancer cells.

In recent years, T-cell receptors have become promising immunotherapeutic factors against cancer. Ross Robinson, David Cole and colleagues (5) focus on how engineering soluble T-cell receptors (TCRs) can aid the development of cancer immunotherapeutics and they also discuss the importance of the balance between enhanced affinity and stability on the one side and high selectivity and specificity on the other side when designing such engineered TCR approaches.

Kristina Riegel, Krishnaraj Rajalingam and colleagues (6) give a comprehensive overview of how the genome can be exploited for cancer drug development and they discuss the role of precision medicine in specifically targeted cancer therapeutics.

The dysregulation of pre-mRNA processing in cancer is reviewed by Claudio Sette and co-authors (7). In this study, factors involved in alternative splicing and polyadenylation, two key steps in pre-mRNA processing, are described as promising therapeutic targets.

In the study by Andrew Massey and colleagues (8), it is shown that replication stress and DNA damage induced by DNA damage response inhibitors result in increased cytoplasmic dsDNA in cancer cells. This in turn activates TBK1, a key effector of the cytosolic DNA sensing pathway. Moreover, the authors discuss the potential mechanisms underlying the observed lack of type I interferon response and how this can influence clinical strategies combining DNA damage response inhibitors with immune checkpoint inhibitors.

Xiangning Fu, Hui Sun and colleagues (9) report that ORM1, in combination with and TGF-β, may be a promising clinical biomarker in the diagnosis of early non-small cell lung cancer (NSCLC).

In the original article by Hongqian Guo and co-authors (10), cancer-associated fibroblasts are found to promote the upregulation of SOX9 in prostate cancer, leading to tumour progression through HGF/c-Met-FRA1 signalling, indicating that SOX9 can be a suitable biomarker for optimal patient enrolment for HGF/c-Met inhibition treatment.

Neil Kelleher and colleagues (11) report oncogenic KRAS-specific proteomic alterations and show that ASS1 expression supports colorectal cancer cell proliferation, suggesting that it would be intriguing to assess the therapeutic potential of ASS1-specific inhibitors.

Mi-Young Kim and colleagues (12) show that combined inhibition of PARP1 and PRC2 in BRCA-proficient triple negative breast cancer results in increased angiogenesis and macrophage differentiation. In this study, a previously unknown synthetic viable interaction between PARP1 and PRC2 which results in a NF-κB-mediated modification of the tumour microenvironment is revealed.

In the original article by Xinzhong Chang, Zhenyi Ma and co-authors (13) SPIB is shown to promote anoikis resistance in lung cancer cells. The authors report that this is mediated by an increase in autolysosomal activity in these cells.

In their original article, which is the Richard Perham Prizewinner 2021, Alberto Muñoz, Antonio Barbáchano and colleagues (14) report that Vitamin D upregulates stemness-related genes and leads to the undifferentiated phenotype in normal organoids, whereas it induces differentiation in tumour organoids. These findings uncover a regulatory role of vitamin D on crypt stem cells, shedding light on a new aspect of colorectal cancer development.

We hope that you enjoy reading this selection of The FEBS Journal articles on cancer research listed here!

Poster image: Cancer cell and lymphocytes (Image taken from Shutterstock, ID: 98612516)

References:

1. Dhillon P & Watson CJ (2021) In Conversation with Christine Watson. FEBS J. https://doi.org/10.1111/febs.16071
2. Kugeratski FG & Kalluri R (2021) Exosomes as mediators of immune regulation and immunotherapy in cancer. FEBS J. Jan;288(1):10-35. https://doi.org/10.1111/febs.15558
3. Damen MPF, van Rheenen J & Scheele CLGJ (2020) Targeting dormant tumor cells to prevent cancer recurrence. FEBS J. https://doi.org/10.1111/febs.15626
4. Yan S & Wan G (2021) Tumor-associated macrophages in immunotherapy. FEBS J. https://doi.org/10.1111/febs.15726
5. Robinson RA, McMurran C, McCully ML & Cole DK (2021) Engineering soluble T-cell receptors for therapy. FEBS J. https://doi.org/10.1111/febs.15780
6. Dupont CA, Riegel K, Pompaiah M, Juhl H & Rajalingam K (2021) Druggable genome and precision medicine in cancer: current challenges. FEBS J. https://doi.org/10.1111/febs.15788
7. Naro C, Bielli P & Sette C (2021) Oncogenic dysregulation of pre-mRNA processing by protein kinases: challenges and therapeutic opportunities. FEBS J. https://doi.org/10.1111/febs.16057
8. Wayne J, Brooks T, Landras A & Massey AJ (2021) Targeting DNA damage response pathways to activate the STING innate immune signaling pathway in human cancer cells. FEBS J. Aug;288(15):4507-4540. https://doi.org/10.1111/febs.15747
9. Ye X, Zhang N, Jin Y, Xu B, Guo C, Wang X, Su Y, Yang Q, Song J, Yu W et al. (2020) Dramatically changed immune-related molecules as early diagnostic biomarkers of non-small cell lung cancer. FEBS J. Feb;287(4):783-799. https://doi.org/10.1111/febs.15051
10. Qin H, Yang Y, Jiang B, Pan C, Chen W, Diao W, Ding M, Cao W, Zhang Z, Chen M et al. (2020) SOX9 in prostate cancer is upregulated by cancer-associated fibroblasts to promote tumor progression through HGF/c-Met-FRA1 signaling. FEBS J. Sep;288(18):5406-5429. https://doi.org/10.1111/febs.15816
11. Doubleday PF, Fornelli L, Ntai I & Kelleher NL (2021) Oncogenic KRAS creates an aspartate metabolism signature in colorectal cancer cells. FEBS J. https://doi.org/10.1111/febs.16111
12. Yang AY, Choi EB, Park MS, Kim SK, Park MS & Mi-Young Kim (2021) PARP1 and PRC2 double deficiency promotes BRCA-proficient breast cancer growth by modification of the tumor microenvironment. FEBS J. May;288(9):2888-2910. https://doi.org/10.1111/febs.15636
13. Zhang H, Wang G, Zhou R, Li X, Sun Y, Li Y, Du W, Yan X, Yang J, Chang X et al. (2020) SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells. FEBS J. Nov;287(21):4696-4709. https://doi.org/10.1111/febs.15272
14. Fernández-Barral A, Costales-Carrera A, Buira SP, Jung P, Ferrer-Mayorga G, Larriba MJ, Bustamante-Madrid P, Domínguez O, Real FX, Guerra-Pastrián L et al. (2020) Vitamin D differentially regulates colon stem cells in patient-derived normal and tumor organoids. FEBS J. Jan;287(1):53-72. https://doi.org/10.1111/febs.14998