Trends in Cancer
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Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

October 5, 2022


Senescent stromal cells: roles in the tumor microenvironment

  • Yael Gabai,
  • Benjamin Assouline,
  • Ittai Ben-Porath
First published:October 05, 2022
Cellular senescence forms a barrier to tumorigenesis, by inducing cell cycle arrest in damaged and mutated cells. However, once formed, senescent cells often emit paracrine signals that can either promote or suppress tumorigenesis. There is evidence that, in addition to cancer cells, subsets of tumor stromal cells, including fibroblasts, endothelial cells, and immune cells, undergo senescence. Such senescent stromal cells can influence cancer development and progression and represent potential targets for therapy.

September 29, 2022


Cancer fitness genes: emerging therapeutic targets for metastasis

  • Minhong Shen,
  • Yibin Kang
First published:September 29, 2022
Development of cancer therapeutics has traditionally focused on targeting driver oncogenes. Such an approach is limited by toxicity to normal tissues and treatment resistance. A class of ‘cancer fitness genes’ with crucial roles in metastasis have been identified. Elevated or altered activities of these genes do not directly cause cancer; instead, they relieve the stresses that tumor cells encounter and help them adapt to a changing microenvironment, thus facilitating tumor progression and metastasis.

September 21, 2022


GOT2 consider the tumor microenvironment

  • Brian T. Do,
  • Matthew G. Vander Heiden
First published:September 21, 2022
To thrive in a hypoxic and nutrient-limited tumor microenvironment, pancreatic ductal adenocarcinoma (PDAC) cells rewire their metabolism. Understanding PDAC cell metabolism may uncover vulnerabilities that can be targeted for improved therapy. Three recent studies find that the PDAC tumor microenvironment modulates the functional consequences of depleting the mitochondrially localized aspartate transaminase GOT2, thus providing new insights into the metabolism of this lethal cancer.

September 15, 2022


Mechanisms of PDAC subtype heterogeneity and therapy response

  • Elisa Espinet,
  • Lukas Klein,
  • Ellen Puré,
  • Shiv K. Singh
First published:September 15, 2022
Pancreatic ductal adenocarcinoma (PDAC) is clinically challenging due to late diagnosis and resistance to therapy. Two major PDAC subtypes have been defined based on malignant epithelial cell gene expression profiles; the basal-like/squamous subtype is associated with a worse prognosis and therapeutic resistance as opposed to the classical subtype. Subtype specification is not binary, consistent with plasticity of malignant cell phenotype. PDAC heterogeneity and plasticity reflect partly malignant cell-intrinsic transcriptional and epigenetic regulation.

September 9, 2022


TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities

  • Keith Garcia,
  • Anne-Claude Gingras,
  • Kieran F. Harvey,
  • Munir R. Tanas
First published:September 09, 2022
The Hippo pathway is dysregulated in many different cancers, but point mutations in the pathway are rare. Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) fusion proteins have emerged in almost all major cancer types and represent the most common genetic mechanism by which the two transcriptional co-activators are activated. Given that the N termini of TAZ or YAP are fused to the C terminus of another transcriptional regulator, the resultant fusion proteins hyperactivate a TEAD transcription factor-based transcriptome.

September 8, 2022


Battle of the γδ T cell subsets in the gut

  • Sofia Mensurado,
  • Bruno Silva-Santos
First published:September 08, 2022
Open Access
In a study in Science, Reis et al. describe a temporal segregation of γδ T cell activities in colorectal cancer (CRC). Initially tumor surveillance is orchestrated by interferon-γ (IFN-γ)-producing and cytotoxic γδ T cell subsets, but once the tumor thrives, it becomes infiltrated by interleukin (IL)-17+ γδ T cell subsets that promote its growth.

Gut microbiota – a double-edged sword in cancer immunotherapy

  • Miles C. Andrews,
  • Ajithkumar Vasanthakumar
First published:September 08, 2022
Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, many patients fail to respond to this therapy or experience side effects. Recently, gut microbiota have emerged as a key determinant of ICB efficacy and toxicity, making manipulation of the microbiome a novel therapeutic strategy with which to improve ICB outcomes.

August 27, 2022


Mitochondrial DNA is a major source of driver mutations in cancer

  • Minsoo Kim,
  • Mahnoor Mahmood,
  • Ed Reznik,
  • Payam A. Gammage
First published:August 27, 2022
Open Access
Mitochondrial DNA (mtDNA) mutations are among the most common genetic events in all tumors and directly impact metabolic homeostasis. Despite the central role mitochondria play in energy metabolism and cellular physiology, the role of mutations in the mitochondrial genomes of tumors has been contentious. Until recently, genomic and functional studies of mtDNA variants were impeded by a lack of adequate tumor mtDNA sequencing data and available methods for mitochondrial genome engineering. These barriers and a conceptual fog surrounding the functional impact of mtDNA mutations in tumors have begun to lift, revealing a path to understanding the role of this essential metabolic genome in cancer initiation and progression.

August 19, 2022


Space in cancer biology: its role and implications

  • Anna Fomitcheva-Khartchenko,
  • Aditya Kashyap,
  • Tamar Geiger,
  • Govind V. Kaigala
First published:August 19, 2022
Tumor cells present complex behaviors in their interactions with other cells. This intricate behavior is driving the need to develop new tools to understand these ecosystems. The surge of spatial technologies allows evaluation of the complexity of relationships between cells present in a tumor, giving insights about tumor heterogeneity and the tumor microenvironment while providing clinically relevant metrics for tumor classification. In this review, we describe key results obtained using spatial techniques, present recent advances in methods to uncover spatially relevant biological significance, and summarize their main characteristics.

August 11, 2022


T cell-mediated additive cytotoxicity – death by multiple bullets

  • Bettina Weigelin,
  • Peter Friedl
First published:August 11, 2022
Open Access
Immune effector cells, including cytotoxic T cells (CTLs), induce apoptosis and eliminate target cells by direct cell–cell contacts. In vivo, CTLs fail to efficiently kill solid tumor cells by individual contacts but rely upon multihit interactions by many CTLs (swarming). Recent evidence has indicated that multihit interactions by CTLs induce a series of sublethal damage events in target cells, including perforin-mediated membrane damage, induction of reactive oxygen species (ROS), nuclear envelope rupture, and DNA damage.

August 3, 2022


The urgent need to improve childhood cancer cachexia

  • Daniel V. Runco,
  • Teresa A. Zimmers,
  • Andrea Bonetto
First published:August 03, 2022
Open Access
Clinical care and research around cancer cachexia in children is lacking. Cachexia increases treatment-related toxicity and long-term morbidity and potentially affects mortality. We highlight the urgent need for specific focus on childhood cancer cachexia and discuss potential solutions to inform cachexia therapeutics for children.

Solving the puzzle of what makes immunotherapies work

  • Xiaoxiao Ma,
  • Timothy A. Chan
First published:August 03, 2022
The rapid adoption of immune checkpoint blockade (ICB) therapies has led to a need to understand the mechanistic drivers of efficacy and the identification of novel biomarkers that enrich for patients who benefit from ICB therapy. Here, we provide a perspective on emerging biomarker candidates, their underlying biological mechanisms, and how they may fit into the current landscape of ICB biomarkers. We discuss new frameworks to identify and evaluate biomarker candidates and review the opportunities and challenges of utilizing biomarker-derived models to facilitate the development of new immunotherapies.

July 29, 2022


Roles of mitochondrial genetics in cancer metastasis

  • Danny R. Welch,
  • Christian Foster,
  • Isidore Rigoutsos
First published:July 29, 2022
The contributions of mitochondria to cancer have been recognized for decades. However, the focus on the metabolic role of mitochondria and the diminutive size of the mitochondrial genome compared to the nuclear genome have hindered discovery of the roles of mitochondrial genetics in cancer. This review summarizes recent data demonstrating the contributions of mitochondrial DNA (mtDNA) copy-number variants (CNVs), somatic mutations, and germline polymorphisms to cancer initiation, progression, and metastasis.

July 28, 2022


Emerging metabolomic tools to study cancer metastasis

  • Luiza Martins Nascentes Melo,
  • Nicholas P. Lesner,
  • Marie Sabatier,
  • Jessalyn M. Ubellacker,
  • Alpaslan Tasdogan
First published:July 28, 2022
Open Access
Metastasis is responsible for 90% of deaths in patients with cancer. Understanding the role of metabolism during metastasis has been limited by the development of robust and sensitive technologies that capture metabolic processes in metastasizing cancer cells. We discuss the current technologies available to study (i) metabolism in primary and metastatic cancer cells and (ii) metabolic interactions between cancer cells and the tumor microenvironment (TME) at different stages of the metastatic cascade.

July 27, 2022


Inflammation: the incubator of the tumor microenvironment

  • Dominic Denk,
  • Florian R. Greten
First published:July 27, 2022
An inflammatory microenvironment, either conferred by an underlying chronic overt or smoldering inflammatory condition constitutes a prerequisite and fuel to essentially all cancers. The complex reciprocal interplay of different cell types in the tumor microenvironment (TME) determines patient outcome. Apart from the actual tumor cells, local and recruited nonmalignant cells as well as the intestinal microbiome actively shape polarization and plasticity of cells in the TME, thereby augmenting protumorigenic and prometastatic inflammatory processes.

July 20, 2022


Revisiting the concept of childhood preleukemia

  • Cesar Cobaleda,
  • Carolina Vicente-Dueñas,
  • Manuel Ramírez-Orellana,
  • Isidro Sanchez-Garcia
First published:July 20, 2022
Preleukemic has been used to describe children with a propensity to develop B cell acute lymphoblastic leukemia (B-ALL). However, leukemia-predisposing mutations can also be present in differentiated cells unable to transform. We postulate that preleukemia should only be used when such mutations arise in progenitors capable of evolving to B-ALL.

July 16, 2022


Therapeutic targeting of regulatory T cells in cancer

  • Feng Shan,
  • Ashwin Somasundaram,
  • Tullia C. Bruno,
  • Creg J. Workman,
  • Dario A.A. Vignali
First published:July 16, 2022
The success of immunotherapy in oncology underscores the vital role of the immune system in cancer development. Regulatory T cells (Tregs) maintain a fine balance between autoimmunity and immune suppression. They have multiple roles in the tumor microenvironment (TME) but act particularly in suppressing T cell activation. This review focuses on the detrimental and sometimes beneficial roles of Tregs in tumors, our current understanding of recruitment and stabilization of Tregs within the TME, and current Treg-targeted therapeutics.

July 13, 2022


Drug independence and the curability of cancer by combination chemotherapy

  • Amy E. Pomeroy,
  • Emmett V. Schmidt,
  • Peter K. Sorger,
  • Adam C. Palmer
First published:July 13, 2022
Open Access
Combination chemotherapy can cure certain leukemias and lymphomas, but most solid cancers are only curable at early stages. We review quantitative principles that explain the benefits of combining independently active cancer therapies in both settings. Understanding the mechanistic principles underlying curative treatments, including those developed many decades ago, is valuable for improving future combination therapies. We discuss contemporary evidence for long-established but currently neglected ideas of how combination therapy overcomes tumor heterogeneity.

July 8, 2022


Decoding endoplasmic reticulum stress signals in cancer cells and antitumor immunity

  • Camilla Salvagno,
  • Jessica K. Mandula,
  • Paulo C. Rodriguez,
  • Juan R. Cubillos-Ruiz
First published:July 08, 2022
The tumor microenvironment (TME) provokes endoplasmic reticulum (ER) stress in malignant cells and infiltrating immune populations. Sensing and responding to ER stress is coordinated by the unfolded protein response (UPR), an integrated signaling pathway governed by three ER stress sensors: activating transcription factor (ATF6), inositol-requiring enzyme 1α (IRE1α), and protein kinase R (PKR)-like ER kinase (PERK). Persistent UPR activation modulates malignant progression, tumor growth, metastasis, and protective antitumor immunity.

July 7, 2022


Age-associated differences in the cancer molecular landscape

  • Kasit Chatsirisupachai,
  • Cyril Lagger,
  • João Pedro de Magalhães
First published:July 07, 2022
Open Access
Cancer is an age-related disease, as incidence and mortality for most types of cancer increase with age. However, how molecular alterations in tumors differ among patients of different ages remains poorly understood. Recent studies have shed light on the age-associated molecular landscapes in cancer. Here, we summarize the main findings of these current studies, highlighting major differences in the genomic, transcriptomic, epigenetic, and immunological landscapes between cancer in younger and older patients.

October 24, 2020


Tele-oncology in the COVID-19 Era: Are Medical Students Left Behind?

(Trends in Cancer 6:10, p:811–812, 2020)

  • Kathrine S. Rallis,
  • Andrea M. Allen-Tejerina
First published:October 24, 2020
In this Letter article, the author’s last name lacked a hyphen and therefore was incorrectly represented. The corrected author name is Andrea M. Allen-Tejerina. This has been corrected in the original online article. The authors apologize for this error.