-
The Intestinal Microbiota and Therapeutic Responses to Immunotherapy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2024-01-25 Pamela S. Herrera, Marcel van den Brink
The intestinal microbiota, a complex ecosystem of microorganisms, has emerged as an important player in modulating various aspects of human health and disease. The microbiota is in a state of constant cross talk with itself and its host, and these interactions regulate several aspects of host homeostasis, including immune responses. Studies have demonstrated a relationship between the microbiota and
-
Small-Molecule Approaches to Target Transcription Factors Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2024-01-12 Huarui Cui, Morgan Stilgenbauer, Angela N. Koehler
Dysregulated transcription factor activity is a defining feature of various cancer types. As such, targeting oncogenic transcriptional dependency has long been pursued as a potential therapeutic approach. However, transcription factors have historically been deemed as undruggable targets due to their highly disordered structures and lack of well-defined binding pockets. Nevertheless, interest in their
-
Therapeutic Discovery for Chromatin Complexes: Where Do We Stand? Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2024-01-12 Dominic D.G. Owens, Matthew E.R. Maitland, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy
In this review, we explore the current landscape of preclinical and clinical therapeutics targeting epigenetic complexes in cancer, focusing on targets with enzymatic inhibitors, degraders, or ligands capable of disrupting protein–protein interactions. Current strategies face challenges such as limited single-agent clinical efficacy due to insufficient disruption of chromatin complexes and incomplete
-
Next-Generation Therapies for Multiple Myeloma Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2024-01-12 Erin W. Meermeier, P. Leif Bergsagel, Marta Chesi
Recent therapeutic advances have significantly improved the outcome for patients with multiple myeloma (MM). The backbone of successful standard therapy is the combination of ikaros degraders, glucocorticoids, and proteasome inhibitors that interfere with the integrity of myeloma-specific superenhancers by directly or indirectly targeting enhancer-bound transcription factors and coactivators that control
-
Therapeutic Targeting of the Menin–KMT2A Interaction Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2024-01-02 Pablo R. Freire, Jevon A. Cutler, Scott A. Armstrong
The direct targeting of chromatin-associated proteins is increasingly recognized as a potential therapeutic strategy for the treatment of cancer. In this review, we discuss a prominent example, namely, small-molecule inhibitors that target the menin–KMT2A interaction. These molecules are currently being investigated in clinical trials and showing significant promise. We describe the unique specificity
-
Applications of Digital Pathology in Cancer: A Comprehensive Review Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2024-01-02 Mohamed Omar, Mohammad K. Alexanderani, Itzel Valencia, Massimo Loda, Luigi Marchionni
Digital pathology, powered by whole-slide imaging technology, has the potential to transform the landscape of cancer research and diagnosis. By converting traditional histopathological specimens into high-resolution digital images, it paves the way for computer-aided analysis, uncovering a new horizon for the integration of artificial intelligence (AI) and machine learning (ML). The accuracy of AI-
-
Allogeneic CAR T Cell Therapy for Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-18 Barbra Johnson Sasu, Elvin James Lauron, Thomas Schulz, Hsin-Yuan Cheng, Cesar Sommer
Autologous chimeric antigen receptor (CAR) T cell therapy, produced from the patient's own T cells, has changed the treatment landscape for hematologic malignancies but has some drawbacks that prevent large-scale clinical application, including logistical complexities in supply, patient T cell health, treatment delays, and limited manufacturing slots. Allogeneic, or off-the-shelf, CAR T cell therapies
-
Biological, Diagnostic, and Therapeutic Insights from (Epi)Genomic Profiling of Pediatric Brain Tumors Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-18 Antonella De Cola, Amelia Foss, Richard Gilbertson, Manav Pathania
Pediatric brain tumors comprise a diverse set of diseases. (Epi)genomic analyses have provided insights into the biology of these tumors, stratifying them into distinct subtypes with different oncogenic driver mechanisms and developmental origins. A feature shared by these tumors is their initiation within neural stem or progenitor cells that undergo stalled differentiation in unique, niche-dependent
-
Relationships Between Regeneration, Wound Healing, and Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-18 Gianna Maggiore, Hao Zhu
Regeneration and cancer share genetic mechanisms and cellular processes. While highly regenerative cells are often the source of cancer, persistent injury or imperfect regeneration in the form of wound healing can lead to degenerative conditions that favor cancer development. Thus, the causal interplay between regeneration and cancer is complex. This article focuses on understanding how functional
-
Extrachromosomal DNA: Biogenesis and Functions in Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-15 Ellis J. Curtis, John C. Rose, Paul S. Mischel, Howard Y. Chang
In cancer, oncogenes can untether themselves from chromosomes onto circular, extrachromosomal DNA (ecDNA) particles. ecDNA are common in many of the most aggressive forms of cancer of women and men and of adults and children, and they contribute to treatment resistance and shorter survival for patients. Hiding in plain sight and missing from cancer genome maps, ecDNA was not, until recently, widely
-
Complex Roles of PTPN11/SHP2 in Carcinogenesis and Prospect of Targeting SHP2 in Cancer Therapy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-06 Alexander Scheiter, Li-Chun Lu, Lilian H. Gao, Gen-Sheng Feng
The nonreceptor tyrosine phosphatase SHP2 has been at the center of cell signaling research for three decades. SHP2 is required to fully activate the RTK/RAS/ERK signaling cascade, although the underlying mechanisms are not completely understood. PTPN11 , which encodes SHP2, is the first identified proto-oncogene that encodes a tyrosine phosphatase, with dominantly activating mutations detected in
-
Basket Trials: Past, Present, and Future Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-06 Yonina R. Murciano-Goroff, Manik Uppal, Monica Chen, Guilherme Harada, Alison M. Schram
Large-scale tumor molecular profiling has revealed that diverse cancer histologies are driven by common pathways with unifying biomarkers that can be exploited therapeutically. Disease-agnostic basket trials have been increasingly utilized to test biomarker-driven therapies across cancer types. These trials have led to drug approvals and improved the lives of patients while simultaneously advancing
-
Deciphering the Warburg Effect: Metabolic Reprogramming, Epigenetic Remodeling, and Cell Dedifferentiation Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-06 Albert M. Li, Jiangbin Ye
A century ago, Otto Heinrich Warburg made a seminal discovery now known as the Warburg effect. This metabolic signature, prevalent across all cancer cells, is characterized by the prominent shift of glucose metabolism toward lactate production instead of oxidative respiration. Warburg's pioneering theory suggested that the induction of the Warburg effect instigates dedifferentiation and the process
-
RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-06 Daniel A. Bonsor, Dhirendra K. Simanshu
Mutations in RAS proteins play a pivotal role in the development of human cancers, driving persistent RAF activation and deregulating the mitogen-activated protein kinase (MAPK) signaling pathway. While progress has been made in targeting specific oncogenic RAS proteins, effective drug-based therapies for most RAS mutations remain limited. Recent investigations into RAS–RAF complexes and the SHOC2–MRAS–PP1C
-
Advances in Therapies Targeting Inhibitory Checkpoint Receptors: TIGIT, LAG-3, and Beyond Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-12-06 Jane A. Healy, Jin-Hwan Han, David Bauché, Tanya E. Keenan, Jose Casasnovas-Nieves, Konstantin Dobrenkov
Progress in our understanding of how tumor cells co-opt immune checkpoint receptor (ICR) regulation of the immune response to suppress T cell function and how these proteins interact in the tumor microenvironment has resulted in the development of a plethora of therapeutic ICR monoclonal antibodies. While anti-CTLA-4 and anti-PD-1/PD-L1 therapies have provided meaningful clinical benefit in patients
-
Stalled CARs: Mechanisms of Resistance to CAR T Cell Therapies Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-04-11 Diego Salas-Benito, Trisha R. Berger, Marcela V. Maus
Chimeric antigen receptor (CAR) T cell therapy has emerged as a new opportunity for cancer treatment; however, resistance can occur due to intrinsic (T cells), extrinsic (tumors), or acquired (tumors) factors. In many cases, the knowledge of these mechanisms comes from clinical observations of patients treated with CAR T cells. In addition, the structure of the CAR molecule and the manufacturing process
-
On the Biology and Therapeutic Modulation of Macrophages and Dendritic Cells in Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-25 Matthew D. Park, Meriem Belabed, Steven T. Chen, Pauline Hamon, Samarth Hegde, Raphaël Mattiuz, Thomas U. Marron, Miriam Merad
Myeloid cells represent a dominant cellular compartment of tumor lesions and play key roles in tumor inception, progression, metastasis, and response to treatment. Mononuclear phagocytes (MNPs), which include dendritic cells and macrophages, are unique among myeloid cells, as they not only shape both the broader composition and state of the tumor microenvironment but can also specifically instruct
-
Next-Generation Estrogen Receptor–Targeted Therapeutics Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-25 Tharu M. Fernando, Heather M. Moore, Matthew J. Wongchenko, Ciara Metcalfe
Estrogen receptor (ER) α is expressed in the vast majority of breast cancers and is one of the most successfully prosecuted drug targets in oncology, with multiple classes of endocrine therapies approved for the treatment of ER+ breast cancer. These existing agents are highly active, both as single agents and as combination partners for other targeted therapies, and have significantly benefited patients
-
The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-25 Joelle P. Straehla, David A. Reardon, Patrick Y. Wen, Nathalie Y.R. Agar
The blood-brain barrier is critically important for the treatment of both primary and metastatic cancers of the central nervous system (CNS). Clinical outcomes for patients with primary CNS tumors are poor and have not significantly improved in decades. As treatments for patients with extracranial solid tumors improve, the incidence of CNS metastases is on the rise due to suboptimal CNS exposure of
-
Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-25 Tijana Martinov, Philip D. Greenberg
T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers and tumor suppressors
-
AI in Computational Pathology of Cancer: Improving Diagnostic Workflows and Clinical Outcomes? Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Didem Cifci, Gregory P. Veldhuizen, Sebastian Foersch, Jakob Nikolas Kather
Histopathology plays a fundamental role in the diagnosis and subtyping of solid tumors and has become a cornerstone of modern precision oncology. Histopathological evaluation is typically performed manually by expert pathologists due to the complexity of visual data. However, in the last ten years, new artificial intelligence (AI) methods have made it possible to train computers to perform visual tasks
-
Somatic Mutations in Normal Tissues: New Perspectives on Early Carcinogenesis Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Albert Herms, Philip H. Jones
Normal tissues progressively acquire mutations. Some mutations are positively selected, driving clonal expansions that may colonize the majority of a tissue by old age. In several cases mutant clonal expansion is due to biasing stem cell fate toward proliferation. However, the expansionary phase is transient and is followed by reversion toward wild-type behavior so that normal tissue integrity is retained
-
Cancer-Associated Fibroblasts: Lessons from Pancreatic Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Mara H. Sherman, Marina Pasca di Magliano
Cancer-associated fibroblasts (CAFs) are present in all malignancies. Arguably, in none are they as prevalent as they are in pancreatic ductal adenocarcinoma (PDAC), where they often outnumber cancer cells. The origin and function of CAFs are still not completely understood, and attempts to target this cell population as a component of combination therapy have so far not succeeded. Our understanding
-
Engineering the Immune Microenvironment into Organoid Models Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Kathleen A. Luckett, Karuna Ganesh
Organoid models have revolutionized cancer research through their ability to capture the cellular heterogeneity and spatial organization of a tumor in 3D culture. Patient-derived organoids can also mirror responses to therapy in vitro, opening the doors to personalized medicine that can direct clinical decision-making. As cancer immunotherapy has flourished and efforts to develop novel immunotherapies
-
The Potent and Paradoxical Biology of Cellular Senescence in Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Paul B. Romesser, Scott W. Lowe
Cellular senescence is a tumor-suppressive program that promotes tissue homeostasis by identifying damaged cells for immune-mediated clearance. Thus, the ability to evade senescence and the ensuing immune surveillance is a hallmark of cancer. Reactivation of senescence programs can result in profound immune-mediated tumor regressions or sensitize tumors to immunotherapy, although the aberrant persistence
-
Strategies for Heating Up Cold Tumors to Boost Immunotherapies Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Daniel J. Zabransky, Mark Yarchoan, Elizabeth M. Jaffee
Immune checkpoint inhibitors induce significant and durable treatment responses in about 20% of all cancers, but many patients have natural resistance to current immunotherapies. The past decade of technological advances has resulted in large-scale profiling of many cancers and their tumor microenvironments, rapidly expanding our understanding of the mechanisms utilized by tumors to create immune-resistant
-
New Tools for Lineage Tracing in Cancer In Vivo Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Matthew G. Jones, Dian Yang, Jonathan S. Weissman
During tumor evolution, cancer cells can acquire the ability to proliferate, invade neighboring tissues, evade the immune system, and spread systemically. Tracking this process remains challenging, as many key events occur stochastically and over long times, which could be addressed by studying the phylogenetic relationships among cancer cells. Several lineage tracing approaches have been developed
-
The Effects of Clonal Heterogeneity on Cancer Immunosurveillance Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Krijn K. Dijkstra, Yin Wu, Charles Swanton
Intratumor heterogeneity (ITH) is associated with tumor progression in several clinical and experimental settings and contributes to therapeutic resistance. Its relation to cancer immunosurveillance is complex. Clonally heterogeneous tumors are associated with decreased immunosurveillance and are less responsive to immune checkpoint inhibition, but the mechanistic basis underlying these observations
-
CAR NK Cells: The Future Is Now Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Martin J. Raftery, Alexander Sebastian Franzén, Gabriele Pecher
Chimeric antigen receptor (CAR) T cell therapy has been a great success in CD19+ hematological diseases. Natural killer (NK) CAR cells offer an alternative to CAR T cells with an intrinsic potential for universal off-the-shelf cell therapeutics. The choice of cell type and the choice of CAR are both relevant for the feasibility, effectivity, engraftment, persistence, side effects, and safety of the
-
Rationales for Combining Therapies to Treat Cancer: Independent Action, Response Correlation, and Collateral Sensitivity Versus Synergy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Emmett V. Schmidt, Linda Z. Sun, Adam C. Palmer, Cong Chen
The principle of independent drug action proposes that responses to drug combinations result from responses to one or the other of two combining agents, but not both. Explorations of biological pathway interactions in signal transduction and immunobiology as synergy have not been connected to mathematical demonstrations of above–independent action activity, which would define pharmacologic synergy
-
Immune Cell Metabolism and Immuno-Oncology Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-17 Chirag H. Patel, Jonathan D. Powell
With the significant successes of immune checkpoint blockade and adoptive cellular therapy, immunotherapy has now become an established treatment option to effectively treat cancer. However, the full potential of this treatment modality has yet to be realized, as there are many additional mechanisms whereby tumors continue to evade immune destruction. To this end, metabolic reprogramming by cancer
-
The Role of Phase-Separated Condensates in Fusion Oncoprotein–Driven Cancers Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-13 Hazheen K. Shirnekhi, Bappaditya Chandra, Richard W. Kriwacki
Fusion oncoproteins (FOs) resulting from in-frame chromosomal translocations are associated with many aggressive cancers with poor patient outcomes. Several FOs are now understood to perform their oncogenic functions within biomolecular condensates formed through liquid-liquid phase separation (LLPS). Two classes of phase-separating FOs have emerged, those that form nuclear condensates and alter chromatin
-
Reinventing Radiobiology in the Light of FLASH Radiotherapy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2023-01-11 Charles L. Limoli, Marie-Catherine Vozenin
Ultrahigh–dose rate FLASH radiotherapy (FLASH-RT) is a potentially paradigm-shifting treatment modality that holds the promise of expanding the therapeutic index for nearly any cancer. At the heart of this exciting technology comes the capability to ameliorate major normal tissue complications without compromising the efficacy of tumor killing. This combination of benefits has now been termed the FLASH
-
Development of Tissue-Agnostic Treatments for Patients with Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Steven Lemery, Lola Fashoyin-Aje, Leigh Marcus, Sandra Casak, Julie Schneider, Marc Theoret, Paul Kluetz, Richard Pazdur, Julia A. Beaver
In 2017 the FDA (US Food and Drug Administration) approved pembrolizumab, a programmed death 1 (PD-1) inhibitor, for the treatment of unresectable or metastatic, microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) solid tumors, regardless of tumor site or histology. This represented the first approval based on the identification of a biomarker and independent of tumor site.
-
TGFβ: Signaling Blockade for Cancer Immunotherapy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Szu-Ying Chen, Ons Mamai, Rosemary J. Akhurst
Discovered over four decades ago, transforming growth factor β (TGFβ) is a potent pleiotropic cytokine that has context-dependent effects on most cell types. It acts as a tumor suppressor in some cancers and/or supports tumor progression and metastasis through its effects on the tumor stroma and immune microenvironment. In TGFβ-responsive tumors it can promote invasion and metastasis through epithelial-mesenchymal
-
CRISPR Screens to Identify Regulators of Tumor Immunity Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Martin W. LaFleur, Arlene H. Sharpe
Cancer immunotherapies, such as immune checkpoint blockade (ICB), have been used in a wide range of tumor types with immense clinical benefit. However, ICB does not work in all patients, and attempts to combine ICB with other immune-based therapies have not lived up to their initial promise. Thus, there is a significant unmet need to discover new targets and combination therapies to extend the benefits
-
Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Annette Paschen, Ignacio Melero, Antoni Ribas
Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen
-
Gut Microbiota in Colorectal Cancer: Associations, Mechanisms, and Clinical Approaches Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Cayetano Pleguezuelos-Manzano, Jens Puschhof, Hans Clevers
Colorectal cancer (CRC) is associated with the presence of particular gut microbes, as observed in many metagenomic studies to date. However, in most cases, it remains difficult to disentangle their active contribution to CRC from just a bystander role. This review focuses on the mechanisms described to date by which the CRC-associated microbiota could contribute to CRC. Bacteria like pks+ Escherichia
-
Targeting KRAS G12C with Covalent Inhibitors Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Jonathan M.L. Ostrem, Kevan M. Shokat
KRAS is the most frequently mutated oncogene in cancer. Following numerous attempts to inhibit KRAS spanning multiple decades, recent efforts aimed at covalently targeting the mutant cysteine of KRAS G12C have yielded very encouraging results. Indeed, one such molecule, sotorasib, has already received accelerated US Food and Drug Administration approval with phase III clinical trials currently underway
-
Tracing and Targeting the Origins of Childhood Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Tim H.H. Coorens, Sam Behjati
Despite the success of treating childhood cancers with cytotoxic agents, novel therapeutic strategies are required to achieve the next leap in cure rates. A promising avenue may be to target the origin of childhood cancers. Here, we review recent advances in tracing the origins of pediatric tumors. Cancer-to-normal cell comparisons by single-cell mRNA sequencing reveal the fetal state of cancer cells
-
Targeting Solid Tumors with Bispecific T Cell Engager Immune Therapy Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Tara Arvedson, Julie M. Bailis, Carolyn D. Britten, Matthias Klinger, Dirk Nagorsen, Angela Coxon, Jackson G. Egen, Flavius Martin
T cell engagers (TCEs) are targeted immunotherapies that have emerged as a promising treatment to redirect effector T cells for tumor cell killing. The strong therapeutic value of TCEs, established by the approval of blinatumomab for the treatment of B cell precursor acute lymphoblastic leukemia, has expanded to include other hematologic malignancies, as well as some solid tumors. Successful clinical
-
The Metabolic Relationship Between Viral Infection and Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-04-11 Peter J. Mullen, Heather R. Christofk
Viruses are fundamental tools in cancer research. They were used to discover the first oncogenes in the 1970s, and they are now being modified for use as antitumor therapeutics. Key to both of these oncogenic and oncolytic properties is the ability of viruses to rewire host cell metabolism. In this review, we describe how viral oncogenes alter metabolism to increase the synthesis of macromolecules
-
Targeting BET Bromodomains in Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Patrick Trojer
Cancer is frequently dependent on aberrant gene expression programs that might be vulnerable to targeting with novel therapeutics. Bromodomain and extraterminal domain (BET) proteins are powerful transcriptional coregulators often found as part of oncogenic transcriptional programs. The bromodomain functionality of BET proteins is highly druggable, and several product candidates are in clinical testing
-
Oncohistones: Hijacking the Histone Code Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Varun Sahu, Chao Lu
Chromatin dysfunction has been implicated in a growing number of cancers especially in children and young adults. In addition to chromatin-modifying and -remodeling enzymes, mutations in histone genes are linked to human cancers. Since the first reports of hotspot missense mutations affecting key residues at the histone H3 tail, studies have revealed how these so-called oncohistones dominantly (H3K27M
-
Novel Mouse Models for Cancer Immunology Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Kelli A. Connolly, Brittany Fitzgerald, Martina Damo, Nikhil S. Joshi
Mouse models of cancer immunology provide excellent systems in which to study and test biological mechanisms of the immune response against cancer. Historically, these models were designed to have different strengths based on the current major research questions at the time. As such, many mouse models of immunology used today were not originally developed to study current questions in the relatively
-
Cancer Genomic Rearrangements and Copy Number Alterations from Errors in Cell Division Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Cheng-Zhong Zhang, David Pellman
Analysis of cancer genomes has shown that a large fraction of chromosomal changes originate from catastrophic events including whole-genome duplication, chromothripsis, breakage-fusion-bridge cycles, and chromoplexy. Through sophisticated computational analysis of cancer genomes and experimental recapitulation of these catastrophic alterations, we have gained significant insights into the origin, mechanism
-
Caught in a Web: Emerging Roles of Neutrophil Extracellular Traps in Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Xue-Yan He, David Ng, Mikala Egeblad
Neutrophil extracellular traps (NETs) are meshes of DNA decorated with granular proteins that are extruded from neutrophils during immune responses to pathogens. However, excessive NET formation is negatively associated with many diseases, including cancer. NETs contain, for example, proteases, danger-associated molecular patterns (DAMPs), and DNA. These components can act directly on the cancer cells
-
RB1, Cancer Lineage Plasticity, and Therapeutic Resistance Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Letian Zhang, David W. Goodrich
Lineage plasticity, a cell's capacity to switch lineage-restricted gene expression states, is required for normal tissue homeostasis. Cancer lineage plasticity is increasingly observed as a mechanism of resistance to therapy, particularly molecularly targeted therapies. These therapies often owe their superior efficacy to the lineage-restricted nature of their therapeutic target, so cancers can evade
-
Clonal Hematopoiesis: Confluence of Malignant and Nonmalignant Diseases Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-18 Amy E. Lin, Philipp J. Rauch, Siddhartha Jaiswal, Benjamin L. Ebert
Clonal hematopoiesis of indeterminate potential (CHIP) is a state in which somatic mutations in hematopoietic stem cells lead to clonal expansion of blood cells in individuals without hematologic malignancy. The mutated genes, including TET2, DNMT3A, ASXL1, TP53, JAK2, and SF3B1, are also recurrently mutated in myeloid malignancies. Individuals with CHIP have an increased risk of developing a hematologic
-
Single-Cell Epigenomics Reveals Mechanisms of Cancer Progression Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2022-01-10 Lindsay M. LaFave, Rachel E. Savage, Jason D. Buenrostro
Cancer initiation is driven by the cooperation between genetic and epigenetic aberrations that disrupt gene regulatory programs critical to maintaining specialized cellular functions. After initiation, cells acquire additional genetic and epigenetic alterations influenced by tumor-intrinsic and -extrinsic mechanisms, which increase intratumoral heterogeneity, reshape the cell's underlying gene regulatory
-
Cancer Dependencies: PRMT5 and MAT2A in MTAP/p16-Deleted Cancers Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Katya Marjon, Peter Kalev, Kevin Marks
Discovery of targeted therapies that selectively exploit the genetic inactivation of specific tumor suppressors remains a major challenge. This includes the prevalent deletion of the CDKN2A/MTAP locus, which was first reported nearly 40 years ago. The more recent advent of RNA interference and functional genomic screening technologies led to the identification of hidden collateral lethalities occurring
-
Developmental Insights into Lung Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Tushar J. Desai
Lung cancer continues to be the number one cancer killer. Despite a surge of therapeutic advances in recent years, lung cancer remains fatal when it presents at a stage too advanced for surgical resection. In part, this is due to the disappointing reality of inevitable drug resistance in the face of highly effective, mutation-specific chemotherapy and the limited efficacy of immune checkpoint blockade
-
Reeling in the Zebrafish Cancer Models Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Alicia M. McConnell, Haley R. Noonan, Leonard I. Zon
Zebrafish are rapidly becoming a leading model organism for cancer research. The genetic pathways driving cancer are highly conserved between zebrafish and humans, and the ability to easily manipulate the zebrafish genome to rapidly generate transgenic animals makes zebrafish an excellent model organism. Transgenic zebrafish containing complex, patient-relevant genotypes have been used to model many
-
The Role of Epigenetic Mechanisms in B Cell Lymphoma Pathogenesis Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Leandro Venturutti, Ari M. Melnick
The capacity of the adaptive immune system to respond to antigenic challenges relies on rapid diversification, expansion, and functional specialization of mature B cells. To accomplish this, activated B cells are transiently endowed with phenotypes that would normally be suppressed in somatic cells, such as enhanced proliferative potential and tolerance for genomic instability. Acquisition of these
-
The Multifaceted Role of Regulatory T Cells in Breast Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Kevin Kos, Karin E. de Visser
The microenvironment of breast cancer hosts a dynamic cross talk between diverse players of the immune system. While cytotoxic immune cells are equipped to control tumor growth and metastasis, tumor-corrupted immunosuppressive immune cells strive to impair effective immunity and promote tumor progression. Of these, regulatory T cells (Tregs), the gatekeepers of immune homeostasis, emerge as multifaceted
-
The Intriguing Clinical Success of BCL-2 Inhibition in Acute Myeloid Leukemia Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Daniel A. Pollyea, Shanshan Pei, Brett M. Stevens, Clayton A. Smith, Craig T. Jordan
Over the past several decades numerous preclinical and clinical studies have pursued new approaches for the treatment of acute myeloid leukemia (AML). While some degree of clinical response has been demonstrated for many therapies, for the most part, fundamental changes in the treatment landscape have been lacking. Recently, the use of the BCL-2 inhibitor venetoclax has emerged as a potent therapy
-
Personal Neoantigen Vaccines for the Treatment of Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Keerthi Shetty, Patrick A. Ott
Cancer vaccines can generate and amplify tumor-specific T cell responses with the promise to provide long-term control of cancer. All cancer cells harbor genetic alterations encoding neoantigens that are specific to the tumor and not present in normal tissue. Similar to foreign antigens targeted by T cells in infectious disease settings, neoantigens represent the long elusive immunogens for cancer
-
The Bidirectional Relationship Between Cancer Epigenetics and Metabolism Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Luke T. Izzo, Hayley C. Affronti, Kathryn E. Wellen
Metabolic and epigenetic reprogramming are characteristics of cancer cells that, in many cases, are linked. Oncogenic signaling, diet, and tumor microenvironment each influence the availability of metabolites that are substrates or inhibitors of epigenetic enzymes. Reciprocally, altered expression or activity of chromatin-modifying enzymes can exert direct and indirect effects on cellular metabolism
-
Mutant Allele Imbalance in Cancer Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Craig M. Bielski, Barry S. Taylor
The search for somatic mutations that drive the initiation and progression of human tumors has dominated recent cancer research. While much emphasis has been placed on characterizing the prevalence and function of driver mutations, comparatively less is known about their serial genetic evolution. Indeed, study of this phenomenon has largely focused on tumor-suppressor genes recessive at the cellular
-
Cancer Immunotherapy and the Nectin Family Annu. Rev. Cancer Biol. (IF 7.7) Pub Date : 2021-03-04 Robert J. Johnston, Peter S. Lee, Pavel Strop, Mark J. Smyth
It is increasingly clear that the nectin family and its immunoreceptors shape the immune response to cancer through several pathways. Yet, even as antibodies against TIGIT, CD96, and CD112R advance into clinical development, biological and therapeutic questions remain unanswered. Here, we review recent progress, prospects, and challenges to understanding and tapping this family in cancer immunotherapy