Ateneo - UPO

This course offers a comprehensive overview of the molecular and biochemical mechanisms underlying cancer development. Students will examine the principal processes of carcinogenesis and the genetic basis of tumor initiation and progression. The course will focus on dysregulated signal transduction pathways involved in cell proliferation, apoptosis, invasiveness, and metastasis. A specific section will address cancer metabolic reprogramming, highlighting its role both in tumor onset and as a mechanism of resistance to anticancer therapies, including targeted therapy, and immunotherapy. The course will also explore the molecular and biochemical circuits mediating tumor–host interactions. Additionally, students will be introduced to key cellular, molecular, and biochemical techniques used to study cancer progression, treatment response, and strategies for prevention.

The teaching material (slides of the lessons) offered on the DIR platform of the course is an additional support to the course. Material for any further information will also be suggested during the course, including specific papers describing and analyzing the tumor processes described during the course. Suggested book "The biology of cancer" of R. Weinberg, 3rd edition; Biologia molecolare della cellula. Sesta edizione. Alberts, Settima edizione Zanichelli

The course will offer an in-depth analysis of the cellular, molecular, and biochemical processes underlying cancer development, highlighting the key hallmarks of tumor biology. By the end of the course, students will be able to: • Describe the molecular and biochemical mechanisms of carcinogenesis. • Identify key genetic and signaling alterations involved in cancer development. • Explain the role of metabolic reprogramming in tumor biology and therapeutic resistance. • Understand the interactions between tumor cells and the host environment. • Apply basic experimental techniques used in cancer research. Moreover, the students will acquire: • ability to understand and critically discuss the literature and present specific part of the program as a research group activity to the colleagues • ability to understand and critically discuss acquired knowledge • communication skills, using appropriate scientific language. Demonstrate that you can communicate effectively both orally and in writing.

Molecular Biology, Biochemistry, Genetics, Cell Biology

The course will include lectures, group research activities in which students will present selected topics to their peers. Hands-on laboratory sessions.

Learning will be monitored through questions put to students during the lessons. The course is supported by the specific DIR section with all the material for the students. Students with physical disabilities, Learning Disabilities (DSA) or Special Education Needs (BES) can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e agli Studenti, consulting the University webpage: https://www.uniupo.it/en/services/services- students-physical-or-learning-disabilities Students with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the tutor in charge of the course to define the examination modalities, concerning academic aspects.

The objective of the exam is to assess the student's level of knowledge and understanding of the course content. The exam consists of a written test designed to evaluate the student’s ability to apply the knowledge acquired during the course. The test includes two types of questions: A) multiple-choice questions and B) open-ended questions. The difficulty level of the questions reflects the topics covered during the course and the reference materials indicated on the DIR platform. Each multiple-choice question (type A) is worth 1 point, while open-ended questions (type B) are worth up to 5 points. The written exam is considered passed if the total score is at least 18 points. During the exam, the use of notes, books, or any other materials is not permitted. To achieve a high score, students must demonstrate independent judgment and critical thinking regarding the topics covered, presenting their answers clearly and logically. The final grade is expressed on a 30-point scale (minimum passing grade: 18). The final evaluation may include a bonus (to be defined) based on group research activities carried out during the course.

The course provides an in-depth overview of cancer development at the biochemical and molecular levels, illustrating the main mechanisms of carcinogenesis and the genetic basis of tumors. Specifically: 1. Cell Proliferation and Death Mechanisms Study of the mechanisms of cell proliferation and cell death (apoptosis), and the molecular alterations of these processes involved in tumorigenesis. Tumor progression as a multistep process: temporal dynamics of tumor development, cancer stem cells, cellular transformation as a cooperative process between oncogenic mutations, mutagenic agents, and promoters. Inflammation and cancer, with a particular focus on alterations in genes (oncogenes/tumor suppressors). Key examples of tumors with mutations in oncogenes and tumor suppressors. The role of p53 in apoptosis; intrinsic and extrinsic apoptosis; necrosis. Immortalization and the telomere: mechanisms involved in cellular and tissue senescence, senescence and telomere dynamics, telomere and transformation. 2. Signal transduction in Cancer General principles of cell signaling; signaling via G protein-coupled receptors; enzyme-linked receptor signaling. Signal transduction and transformation: the role of proto-oncogenes in transformation, receptor and cytoplasmic tyrosine kinases, mechanisms of constitutive activation of signal transduction in tumors. Cytoplasmic signaling pathways controlling various tumor-related processes: the role of mitogenic signals in tumors, the Ras pathway as a key driver of transformation, with a focus on the altered MAP kinase pathway. Invasiveness and metastasis promoted by altered signaling pathways. Targeted molecular therapies. 3. Metabolic Reprogramming in Cancer Analysis of metabolic reprogramming in cancer cells as a hallmark of tumor development and a target for anticancer compounds. Metabolic plasticity, the Warburg effect, mitochondrial dysfunction and the role of mitochondria in transformation, the role of glutamine in proliferation and cell cycle regulation, alteration of NAD biosynthesis pathways, and tumor metabolism as a therapeutic target. 4. Tumor Microenvironment and Cross-Talk Mechanisms Study of cross-talk between tumor cells and the tumor microenvironment (including immune cells such as neutrophils and macrophages, adipocytes, fibroblasts, endothelial cells). Immunotherapy. Focus on malignant pleural mesothelioma as a case study of tumor–host interaction and chronic inflammatory microenvironment. 5. Therapy Resistance Mechanisms Analysis of resistance mechanisms to therapies, with a focus on metastatic melanoma as an example. A section of the lesson will also be dedicated to gender-specific oncology therapies, with a focus on both gender-related differences and cancers specific to males and females. 6. Experimental Methods and Techniques in Cancer Research Analysis of major methods and techniques used to study altered tumor processes: 2D and 3D cancer cell cultures; co-culture systems involving cancer and stromal cells, or cancer and immune cells; flow cytometry-based characterization. Cell viability assays (MTT assay, clonogenic assay). Cell motility/invasiveness assays (transwell, scratch test). Mitochondrial function, glycolysis, and oxidative stress analysis (flow cytometry, colorimetric assays), bioenergetics. Protein analysis (Western blotting, ELISA, immunostaining). RNA analysis (RT-PCR), gene overexpression (transfection), and gene silencing (RNA interference). Selected techniques will be practiced during laboratory exercises.

Knowledge and understanding: acquisition of in-depth knowledge of the biological basis of tumorigenesis and cancer progression: alteration of molecular mechanisms, signal transduction and metabolic pathways. Knowledge of the concepts and applications of molecular biology and biochemistry of tumors and acquisition of appropriate scientific language. -Applied knowledge and comprehension skills: at the end of the course, the student will acquire the ability to apply theoretical knowledge to the execution and understanding of laboratory experiments and to the interpretation of the results obtained. The ability to collect, read, organize scientific literature on selected topics and report the topic to classmates. -Autonomy of judgment: ability to critically analyze the elements related to tumour biology. -Communication skills: use an appropriate scientific lexicon, describe scientific topics related to cancer biology, with a logical and rational approach. -Learning ability: Ability to use teaching materials for a critical and reasoned study.