Cellular plasticity describes the ability of cells to switch their phenotype in response to
microenvironmental changes. It is a key phenomenon in pancreatic ductal adenocarcinoma (PDAC) esentially adding to the tumors high degree of heterogeneity, aggressiveness and therapy resistance. Furthermore, PDAC is characterized by a profound inflammatory stroma which is an important driver of...
Authors: M. Andersen, H. Hasselbalch, T. Stiehl, J.T. Ottesen
Human blood cell production is maintained by hematopoietic stem cells (HSC) which give rise to all types of mature blood cells. Experimental observation of HSC in their physiologic bone-marrow microenvironment, the so-called stem cell niche, is challenging. Therefore, the details of HSC dynamics and the cellular interactions in...
The traditional clonal evolution model integrates genetic mutations and clonal selection but often neglects the critical role of phenotypic plasticity. In this study, we combine longitudinal whole-genome sequencing and flow cytometry data to investigate the progression of chronic lymphocytic leukaemias with bimodal CD49d expression, a prime example of complex clonal evolution. We introduce a...
Authors: Lisa-Marie Philipp, Axel Künstner, Anne-Sophie Mehdorn, Charlotte Hauser, Jan-Paul Gundlach, Olga Will, Sören Franzenburg, Hendrike Knaack, Udo Schumacher, Hauke Busch, Susanne Sebens
Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis and overall survival. Metastasis requires strong cancer cell...
Metabolic stress is a frequent adverse event in tumors caused by mutations, malperfusion, hypoxia, and nutrition deficit. The resulting bioenergetic deprivation triggers signaling, mechanical and metabolic adaptation responses in tumor cells to secure survival and adjust migration activity. Using 3D invasion models and preclinical intravital microscopy in mouse models of breast cancer, we...
Authors: Raafat Chalar, Yujie Xiao, Joon-Hyun Song, Naheel Khatri, Jowana Obeid, Andrew Chen, Fabiola Velazquez, Daniel Canal, Yusuf Hannun, Giovanni D'Angello, Mehdi Damaghi
Phenotypic plasticity and metabolic reprogramming in cancer cells are essential for their adaptation to their harsh tumor microenvironment (TME). Pre-existing cell states and phenotypic plasticity can define the...
Authors: Irina Kareva, Jana Gevertz
Despite the revolutionary impact of immune checkpoint inhibition on cancer therapy, the lack of response in a subset of patients, as well as the emergence of resistance, remain significant challenges. Here we explore the theoretical consequences of the existence of multiple states of immune cell exhaustion on response to checkpoint inhibition therapy. In...
Authors: Madhuri Majumder and Samares Pal
An HIV-COVID-19 co-infection dynamics is modelled mathematically assimilating vaccination mechanism that incorporates endogenous modification of human practices generated by the COVID-19 prevalence, absorbing the relevance of treatment mechanism in suppressing the co-infection burden. Envisaging COVID-19 situation, HIV-subsystem is analysed by...
CAR-T therapy, where T cell are genetically modified to respond to CD19-presenting B cells, has revolutionized the treatment of several blood cancers. The immediate effect of this immunotherapy is associated with a significant inflammatory response in the patient, sometimes leading to a tumor that seemingly swells in the days following CAR-T cell injection. This is referred to as...
The tumour microenvironment is characterized by alterations in the molecular and cellular composition, such as the infiltration of immune cells, reprogramming of fibroblasts, changes in ECM composition, changes in oxygen concentrations and pH, and related cell phenotype changes such as metabolic reprogramming or the emergence of migratory and invasive cancer cells. Critically, many, if not...
Treatment resistance is a major obstacle in cancer treatment. While whole-genome sequencing revealed that single mutations are sometimes sufficient to explain resistance, recent studies demonstrate that more often resistance is a multi-factorial process including non-genetic mechanism. In particular, epigenetic and phenotypic changes that take place at higher frequencies than the acquisition...
Cell plasticity refers to the ability of cells to change their identity or function in response to internal or external cues. This remarkable ability is traditionally associated with embryonic development, where stem cells and progenitors choose from multiple downstream fates to form specialized, functional tissues and organs. Under normal conditions, cell fate commitments are stable, ensuring...
Tumor heterogeneity significantly complicates cancer treatment and prognosis.
Our recent findings demonstrate that the transcriptional dosage of the oncogenic form of the KRAS gene drives tumor evolution in lung adenocarcinoma. Using mouse models, CRISPR activation screens, and chromatin profiling, we showed that - despite being already mutated and copy-number amplified - a mild...
Acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow produces too many lymphocytes without further differentiation into mature blood cells. The primary treatment for most ALL cases is chemotherapy; however, after the intense treatment phase, relapse is observed in some patients. Early-stage relapses might be due to some remaining leukemia cells not being detectable...
Authors: B Vibishan, Paras Jain, Vedant Sharma, Kishore Hari, Jason T George, Mohit Kumar Jolly
Cancer is a heterogeneous disease and variability in drug sensitivity is widely documented across cancer types. Adaptive therapy is an emerging modality of cancer treatment that leverages this heterogeneity in drug resistance to achieve better therapeutic outcomes. Current treatments typically...
Micronenvironmental signals play an important role in controlling cell
phenotypes. A complex network of interactions, both between a cell and
its environment as well as within a cell, govern cell development
processes. Mathematical models can contribute to our understanding of
such processes and support experimental design by generating testable
hypotheses. In this talk, I highlight the...
Phenotypic adaptation, the ability of cells to change phenotype in response to external pressures, has been identified as a driver of drug resistance in cancer. To quantify phenotypic adaptation in BRAFV600E-mutant melanoma, we develop a theoretical model that emerges from data analysis of WM239A-BRAFV600E cell growth rates in response to drug challenge with the BRAF-inhibitor encorafenib. Our...
Early cutaneous squamous cell carcinomas (cSCCs) generally show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits associated with tumor relapse, metastasis, and poor survival. The mechanisms involved in cSCC progression are unclear, and the established markers are suboptimal for accurately predicting the clinical course of the disease....
Authors: Frederick J.H. Whiting, Maximilian Mossner, Calum Gabbutt, Christopher Kimberley, Chris P Barnes, Ann-Marie Baker, Andrea Sottoriva, Richard A. Nichols, Trevor A Graham
Effective cancer treatment frequently fails due to the evolution of drug resistant cell phenotypes caused by underlying genetic or non-genetic changes. The origin of these adaptations, their timing and rate of...
Authors: Chen M. Chen, Rosemary Yu
Plasticity is the potential for cells or cell populations to change their phenotypes and behaviours in response to internal or external cues. Plasticity is fundamental to many complex biological processes, yet to date there remains a lack of mathematical models that can elucidate and predict molecular behaviours in a plasticity programme. Here we report a...
Authors: Gopinath Sadhu, Helen M Byrne, and D C Dalal
Oxygen heterogeneity is a common feature in solid tumors. Oxygen deficiency in a tumor can trigger various events such as metabolic adaptation, angiogenesis, and epithelial-to-mesenchymal transition (EMT), which contribute to the invasion process. In this work, we propose a mathematical model to describe how oxygen levels within a tumor...
Authors: Kevin Flores, Adam Malik, Kyle Nguyen, John Nardini, Cecilia Krona, and Sven Nelander
In the study of brain tumors, patient-derived three-dimensional sphere cultures provide an important tool for studying emerging treatments. The growth of such spheroids depends on the combined effects of proliferation and migration of cells, but it is challenging to make accurate distinctions...
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a promising option for relapsed or refractory lymphoma patients and acute leukemias. Mathematical modeling offers a valuable tool for investigating the interactions among these living drugs, tumors, and heterogeneous patients' immune or inflammatory context. Using longitudinal data from experiments and the clinic, we examine how...
Authors: Oluwafemi Samson OLAGBAMI, Emmanuel Afolabi BAKARE
Soil-transmitted helminthiasis (STH) is major public health challenge in many region of Nigeria, particularly Ogun State. Environmental and climatic factors such as temperature, rainfall and soil pH have been identified to influence the transmission of infectious diseases which include neglected tropical diseases (NTDs). These...
Authors: Helal Ahmed1,2, Luca Heinemann1, Klara Möllers1, Zhangman Wang2, Marah Hussein2, Pradeep Kumar Patnana1,2, Jan Vorwerk1,2, Ashok Kumar Rout3, Eva Dazert, Ulrich Guenther3, Nikolas von Bubnoff2, Wael Mansour4, Cyrus Khandanpour1,2.
Background: Multiple myeloma (MM) is a hematological malignancy that disrupts the bone marrow (BM) microenvironment to support its progression....
Natural selection plays a critical role in the evolution of cancer cells, driving their adaptation and survival within the tumor microenvironment. Cancer arises from genetic and epigenetic alterations that confer selective advantages to certain cells, allowing them to proliferate, evade immune responses, and resist therapies. Within a heterogeneous tumor population, selective pressures such as...
