Blog
2023
Double Trouble for Cancer Tumors
Cancer immunotherapy drugs called PD-1 inhibitors are widely used to stimulate the immune system to fight cancer, but many patients either don’t respond or develop resistance to them. A new small-molecule drug candidate being tested in an early-stage clinical trial aims to improve patient responses to immunotherapy. Check the paper in Nature.
New cancer-killing pill annihilates tumors
Gu et al. check this paper used crystallography-directed medicinal chemistry to identify a small molecule ligand of PCNA that interferes with the resolution of transcription replication conflicts. This compound was found to be orally active and inhibited tumor growth in animals without causing any discernable toxicity even at 6 times its effective dose
Exhaustion-associated cholesterol deficiency dampens the cytotoxic arm of antitumor immunity
In this new paper, the author identified the key regulators of T cell cholesterol deficiency in the TME and revealed the mechanism by which cholesterol deficiency drove T cell exhaustion and dysfunction. A new cholesterol-modulation strategy has been developed to improve the performance of CAR-T cells in treating solid tumor.
In this new paper Generation of spatially resolved gene expression patterns in tumors from patients with ovarian cancer surviving more than 10 years allows the identification of novel predictive biomarkers and therapeutic targets for better patient management.
Machine learning (ML) is increasingly used in clinical oncology to diagnose cancers, predict patient outcomes, and inform treatment planning. In this leading edge paper, the authors reviewed recent applications of ML across the clinical oncology workflow.
Various cell-free DNA (cfDNA) features including methylation and genomic profiles migth be useful for detection of cancer. The authors of a new paper published in Cancer Research, have developed deep learning models based the data generated by the enzymatic conversion based whole methylome sequencing of cfDNA.
Artificial Intelligence in Cancer Research and Precision Medicine
AI has the potential to dramatically affect nearly all aspects of oncology—from enhancing diagnosis to personalizing treatment and discovering novel anticancer drugs. In a new review published in the journal Cancer Discovery, the authors reviewd the recent enormous progress in the application of AI to oncology, highlight limitations and pitfalls, and chart a path for adoption of AI in the cancer clinic.
Pediatric solid and central nervous system tumors are the leading cause of cancer-related death among children. In a new paper, the authors established a single-site collection of 261 cell lines, including 224 pediatric cell lines representing 18 distinct extracranial and brain childhood tumor types. They subjected 182 cell lines to multi-omics analyses (DNA sequencing, RNA sequencing, DNA methylation), and in parallel performed pharmacological and genetic CRISPR-Cas9 loss-of-function screen...
Integrative pan-cancer genomic and transcriptomic analyses of refractory metastatic cancer
Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, Pradat et al Paper analyzed a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. They have demonstrated that molecular markers improve six-month survival prediction, particularly in patients with advanced breast cancer.
Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia
In this paper, Loukas et al. show that loss of many epigenetic regulators, frequently mutated across cancer types, promote subclone expansion by conferring resistance to stressful environments. Epigenetically disrupted cells fail to efficiently rewire transcription in response to stress, lowering the probability of cell death at early stages and favoring stochastic population adaptation.
Metabolic programming and immune suppression in the tumor microenvironment
Increased glucose metabolism and uptake are characteristic of many tumors and used clinically to diagnose and monitor cancer progression. In addition to cancer cells, the tumor microenvironment (TME) encompasses a wide range of stromal, innate, and adaptive immune cells. Cooperation and competition between these cell populations supports tumor proliferation, progression, metastasis, and immune evasion. In this new Review Paper, the authors discussed how metabolic programming of cells within...
Now we know that how Cancer cells shrink or grow larger to survive
A new study, is using advanced image analysis and DNA/protein examination to investigate the size regulation of melanoma cells. It Was found that up-regulation of TP53 or CDKN1A/p21CIP1 is characteristic of proliferative cancer cells with senescent-like sizes/proteomes.
Neutrophil-activating therapy for the treatment of cancer
A new study in the journal “Cancer Cell” suggested a new approach to induce neutrophil-mediated oxidative damage follwoed by T cell-independent tumor clearance.
Detecting liver cancer using cell-free DNA fragmentomes
Screening individuals at high-risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, whole-genome cell-free DNA fragmentome analyses was used to eveluate the possibility of uusing Cell-Free DNA Fragments for early detction of cancer. Using a machine learning model that incorporated multi-feature fragmentome data, the sensitivity for detecting cancer was 88% in an average risk population ...
Neutrophil-activating therapy for the treatment of cancer
Surprisingley, neutrophils are often promote immunosuppression, tumor growth, and metastasis. This new paper demontsrates that neutrophils can be harnessed to induce eradication of tumors and reduce metastatic seeding through the combined actions of tumor necrosis factor, CD40 agonist, and tumor-binding antibody.
Extracellular fluid viscosity enhances cell migration and cancer dissemination
A new study published in Nature has identified a mechanism that allows cancer cells to spread throughout the body. Cancer cells move faster when they are surrounded by thicker fluids, a change that occurs when lymph drainage is disrupted by a primary tumor. These findings provide a potential new target for stopping metastasis, which is responsible for 90% of cancer deaths.
Cancer cells can change size to evade treatment
Almost all living cells maintain size uniformity through successive divisions. Proteins that over and underscale with size can act as rheostats, which regulate cell cycle progression. New study papercombined biochemical profiling technology with mathematical work to show how genetic changes lead to differences in the size of cancer cells.
Cancer fitness genes, emerging therapeutic targets for metastasis
Cancer metastasis is an extremely inefficient process that is limited by numerous stresses tumor cells encounter during the progression from early-stage cancer to metastatic lesions in distant organs. A class of genes, termed ‘cancer fitness genes’, relieve such stresses to facilitate the development of metastatic disease.(see this paper)
Cellular senescence is immunogenic and promotes anti-tumor immunity
Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. In This paper, the authors show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DCs) and antigen-specific CD8 T cells.
Human Cancer Genomes Display Recurrent Repeat Expansions
Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer. New findings Ref suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and provide a comprehensive catalogue for further study.
Multiple Myeloma (MM) develops from well-defined precursor stages, however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. A new paper developed a novel approach, MinimuMM-seq, which enables detection of translocations and copy number abnormalities through whole-genome sequencing of highly pure CTCs.
2022
Heterogeneous HER2 Amplification—a New Clinical Category of HER2-Positive Breast Cancer?
HER2 amplification heterogeneity is associated with resistance to trastuzumab emtansine in the neoadjuvant setting, emphasizing the importance of assessing whether heterogeneous HER2-positive cancers require different treatment pathways. See related paper in Cancer Discovery.
A new road for effective immune checkpoint blockade in breast cancer?
Immune checkpoint blockade (ICB) has revolutionized the landscape of cancer treatment. Nevertheless, most cancer patients still do not respond to ICB. This paper demonstrates the critical role of eosinophils in ICB response and provides proof-of-principle for eosinophil engagement to enhance ICB efficacy.
Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
In melanoma, predicting which tumors will ultimately metastasize guides treatment decisions. Transcriptional signatures of primary tumors have been utilized to predict metastasis, but which among these are driver or passenger events remains unclear. A new paper revealed GRAMD1B, a cholesterol transfer protein, as a bona fide metastasis suppressor, with a majority of knockout animals rapidly developing metastasis.
Metabolic symbiosis in pancreatic cancer
Pancreatic cancer cells exists within a heterogenous and complex microenvironment that imposes limited nutrient availability. New paper now shown that there are two distinct metabolic configurations, facilitating symbiotic intratumoral crosstalk to support survival and growth.
Mutations in epigenetic regulators bring fitness to Cancer
Mutations in epigenetic regulators are prevalent in cancer, but their functional impact is poorly delineated aside from disrupting differentiation. Loukas, Simeoni, et al. paper zoom in on the late occurring, subclonal subset of such mutations and define the molecular mechanism behind their enrichment in cancer.
High-performance multiplex drug-gated CAR circuits
Chimeric antigen receptor (CAR) T cells can revolutionize cancer medicine. However, overactivation, lack of tumor-specific surface markers, and antigen escape have hampered CAR T cell development. A multi-antigen targeting CAR system regulated by clinically approved pharmaceutical agents is needed. Li et al paper has developed a multiplex CAR circuits with advanced functionalities.
Loss of epigenetic regulators accelerated tumorigenesis and revealed lineage infidelity and aberrant expression of alveogenesis genes as potential early events in tumorigenesis. Infrequently mutated genes comprise most of the mutational burden in breast tumors. In this Paper an in vivo CRISPR screening was used to identify functional tumor suppressors realted epigenetic regulation. Loss of epigenetic regulators accelerated tumorigenesis and revealed lineage infidelity and aberrant expression...
Evaluation of cell-free DNA approaches for multi-cancer early detection
cTAF accounts for cfDNA cancer signal variation across cancer types and stages. This new paper has found that cfDNA methylation was the most promising genomic feature for cancer signal detection. The results informed the development of a cfDNA-based multi-cancer early detection test. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approach...
Hallmarks of Cancer-New Dimensions
The hallmarks of cancer paper is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles.As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements.Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitut...
Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. In this new paper probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, They have provided an integrated analysis of CAF subpopulations over a complex spatial transc...
TLR2 is associated with improved survival and premalignant regression in NSCLCin melanoma
This new paper in Cell Reports discusses the usibility of TLR2 expression for survival analysis in NSCLCin melanoma patients. They showed that TLR2 is highly expressed in tumor epithelium and correlates with improved survival and clinical regression
Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma
Immunotherapy presented new hopes for melanoma patients; however, resistance to this therapy is an issue for many patients. Zhou et al. see the paperpropose a mechanism for signal-regulatory protein α1 (SIRPα) expression and describe how its loss may contribute to immunotherapy resistance.
Machine Learning to predict the outcome of breast cancer therapy
In this new paper, the authors collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumours from 168 patients treated with chemotherapy with or without HER2 (encoded by ERBB2)-targeted therapy before surgery. They have established that the response to therapy is determined by the baseline characteristics of the totality of the tumour ecosystem captured through data integration and machine learning. This approach could be used to develo...
Towards next generation precision oncology
Combining omics and 3D-PTA readouts may lead to more accurate clinical predictors and finally accelerate new treatments. A new paper discusses how to do that in action.
Artificial intelligence for multimodal data integration in oncology
A new paper discusses the use of AI for data integration in oncology. They examine challenges in clinical adoption and discuss emerging solutions.
Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue
Genome-wide mutation analyses have revealed that specific anti-cancer drugs are highly mutagenic to cancer cells, but the mutational impact of anti-cancer therapies on normal cells is not known. While chemotherapies are highly effective at killing cancer cells, their systemic use also increases the mutational burden of long-lived normal stem cells responsible for tissue renewal thereby increasing the risk for developing second cancers.paper
The evolutionary dynamics of extrachromosomal DNA in human cancers
Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. In a new paper in Nature, Lange et. al. demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment.
Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. In a new paper, Wang et. al. found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice a...
The importance of ancestry to understanding tumor mutation burden in cancer
New paper In a new paper, Nassar and colleagues find that in solid tumors, tumor-only sequencing leads to an overestimate of the biomarker tumor mutation burden (TMB), particularly in patients of African or Asian ancestry. Correction of the TMB estimate improves the correlation between TMB and response to immunotherapy. Paper in Cancer Cell
Multimodal data fusion improves prognostic models for a majority of cancer types
New paper In a new paper entitled “Pan-cancer integrative histology-genomic analysis via multimodal deep learning”, the authors combined multi types of data to get a better model for prediction Paper in Cancer Cell
Cancer vaccines-the next immunotherapy frontier
New paper A new review discusses the story behind almost 20 years of cancer vaccines and what is the next frontiers in this subject. paper
Advanced multi-omics tumor profiling in precision oncology
New paper New review on the application of the multi-omics tumor profiling in future oncology The paper in Cancer Cell. The authors summarize the latest advances in multi-omics tumor profiling, focusing on spatial genomics and chromatin organization, spatial transcriptomics and proteomics, liquid biopsy, and ex-vivo modeling of drug response.
Cancer cells ‘forced’ to become healthy
New paper Cancer cells have been converted into healthy cells using AI-based data analysis technology. Look at this paper in Nature.
Self-assembling molecules suffocate cancer cells within hours
New paper By deploying a newly-developed drug against a key energy source of cancer cells, scientists at the Max Planck Institute for Polymer Research have developed a new way of eliminating them in mere hours. paper
Race is a key determinant of the human intratumor microbiome
New paper Intratumor microbes, which are present in both tumor and immune cells, have been shown to have multiple effects on human cancer. However, the full scope of usch effect is unknown. In this new paper, the authors find that race is a deterministic factor in thois regard.
Lymph node–targeting delivery of mRNA cancer vaccine
New paper Current messenger RNA (mRNA) vaccines in the clinic were reported to induce side effects in the liver. a lymphoid-organ–specific mRNA vaccine could be a promising strategy for developing next-generation mRNA vaccines See the paper
The gene that causing human disease
New paper Identification of causal genes within the human genome has been one of the biggest challenges in the genomics studies. Collins et al. perform a meta-analysis of almost a million individuals to identify dosage-sensitive segments and genes conferring risk for a range of disease phenotypes. See the paper
New paper Cellular deconvolution algorithms virtually reconstruct tissue composition by analyzing the gene expression of complex tissues. We present the decision tree machine learning algorithm, Kassandra, trained on a broad collection of >9,400 tissue and blood sorted cell RNA profiles incorporated into millions of artificial transcriptomes to accurately reconstruct the tumor microenvironment (TME). See more in this paper
Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo
New paper Cancer growth is accompanied by changes to the extracellular environment of tumors, which aids the proliferation and spread of cancer cells. Cancer-associated extracellular matrix changes include excessive degradation of heparan sulfate carbohydrates, promoting metastatic spread by multiple mechanisms. Heparanase is the main human enzyme responsible for extracellular heparan sulfate breakdown and strongly drives metastasis when overexpressed. See more in this paper
Akt protein boosts cancer metabolism through a two-pronged attack
New paper Mutated forms of the protein Akt can be central drivers of cancer metabolism. A new paper discusses mechanism by which Akt promotes synthesis of the metabolic molecule coenzyme A in cancer.
Glioblastoma hijacks neuronal mechanisms for brain invasion
New paper A new paper demonstrated that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation corresponds to neuronal and neural-progenitor-like tumor cell states, as defined by single-cell transcriptomics, both in mouse models and in the human disease.
New epigenetic regulators of T cell exhaustion
New paper T cell exhaustion limits antitumor immunity, but the molecular determinants of this process remain poorly understood. Belk et al. find several genes related to epigenetic modification and show that by eliminating Arid1a, CD8+ T cells retain proliferative and cytotoxic function in vivo, leading to better anti-tumor activity.
The entire protein universe (AI predicts shape of nearly every known protein)
New paper DeepMind’s AlphaFold tool has determined the structures of around 200 million proteins. See the paper
Targeting drug-resistant brain cancer using new drugs
New paper Lin et al. designed TMZ analogs to overcome drug resistance in GBM. These agents generate a primary DNA lesion that can be repaired by healthy cells with intact DNA repair mechanisms. However, cancer cells that lack DNA-repair machinery are not able to repair the damage that results in selective tumor cell killing
Cancer cells in lymph node rewire the immune system to enable further metastases
New paper Lymph node metastases can suppress the immune system, thereby generating a cancer-permissive environment and promoting metastasis according to this paper.
Aging lung awakens melanoma metastases
New paper In a recent paper it has been established that WNT5A is the central, age-sensitive regulator of the dormancy-to-reactivation axis of melanoma. It has been shown that aged fibroblasts in the lungs suppress WNT5A signaling induced at the primary tumor site to awaken dormant melanoma cells and promote the outgrowth of metastases.
Targeting the tumor microenvironment
New paper Cancer-associated fibroblasts (CAFs) are stromal cells with important roles in modulating tumorigenesis, tumor progression, and responses to therapy. New findings dicussed in this paper
Series on Cancer Immunotherapy
New paper With advances in cancer immunotherapy, Nature put together some of the perspective in this filed in a series
New paper Instead of predicting the shapes of naturally occurring molecules, software designs original ones. See this paper
The sequences of 150,119 genomes in the UK Biobank
New paper The analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank is discrbed in this paper
How T cell exhaustion occures?
New paper An atlas of the genetic regulators of T cell exhaustion has been provided in this paper
The proteomes of 949 cancer cell lines across 28 tissue types
New paper New study provide high definition of proteomes across 949 cell lines. New insigth would be extracted soon. paper —
How neoadjuvant checkpoint blockade induces local and systemic tumor immunity
New paper Starting immunotherapy at eraly stages may benefit some patients. It induces local and systemic immunity paper .
How T cell exhaustion limits antitumor immunity
New paper An atlas of the genetic regulators of T cell exhaustion has been provided in this paper
Tissue preferences by cancer cells.
New paper Which tissue is preferred by cancer cell as a new location for metastasis. Recent paper dicusses a that soft tissues are prefered.
New paper Delivery of drugs including mRNA to the rigth location at the rigth time is challenging. Recent paper dicusses a new method on how to do that.
New paper It appears that cancer is awake and more active during sleep. A stricking new discovery in NATURE. link
Updated materials and methods2
new methods2 So, please check this section regurarly on a weekley basis.
2021
new methods This section would serve as a journal cloub. We will review and keep you updated on new development in regards to the most recent publications in the field of Cancer and stem cell biology,…. So, please check this section regurarly on a weekley basis. title: Updated materials and methods2 tags: big data Cancer biology Setm cells author: Hossein Fallahi member: Hossein Fallahi —
NEW findings worth reading
tags:
- big data
- Cancer biology
It appears that cancer is awake and more active during sleep. A stricking new discovery in NATURE: Check this paper