Program

Provisional program of the Conference

OPENING LECTURE:

Beyond apoptosis induction: achieving tumor control by remodeling the cancer phenotype

SESSION 1

ANAKOINOSIS: CORRECTING DYSREGULATED CANCER HOMEOSTASIS FOR LONG-TERM TUMOR CONTROL

1.A. Clinical trials: Re-directing the flux of information in cancer tissue (i.e., anakoinosis)

  • Hematologic neoplasia
    • Acute/chronic myelocytic leukemia
    • Myelodysplastic syndrome
    • Multiple myeloma
    • Non-Hodgkin lymphoma
  • Metastatic cancer
    • Non-small cell lung cancer
    • Pediatric tumors
    • Hepatocellular carcinoma
    • Pancreatic cancer
    • Angiosarcoma

1.B. Mechanisms of metastatic tumor control: remodeling cancer phenotype beyond apoptosis

  • Principles at the basis of anakoinosis effects
  • Reprogramming tumor tissue
  • Biologic memory
  • Microenvironment and tumor fate
  • Fate of cancer cells: beyond apoptosis
  • Differentiation
  • Trans-differentiation
  • Epithelial-to-mesenchymal transition
  • Changes in the microenvironment
  • Anti-inflammation
  • Immune evasion
  • Clinical implications
  • Therapy sequence: Progression-free survival 2 (PFS2)
  • Overcoming poor risk parameters
  • Histologically different tumors share communication lines as targets for tumor control
  • Metronomic therapies: Reprogramming of cancer tissue

1.C. Anakoinosis: not only cancer

  • Spread of synovial fibroblasts in rheumatoid arthritis

1.D. Reverse Anakoinosis: how carcinogenesis may arise from combination of modulators with no pro-cancerous monoactivity

  • Concerted low-dose exposure to chemical mixtures

1.E. Search for systemic signature of cancer

  • Hint on anakoinosis mechanisms from analysis of patients’ samples       
  • Serum/plasma proteomics and lipidomics

SESSION 2

BIOLOGICAL BASIS OF ANAKOINOSIS: NORMAL AND CANCER TISSUE DYNAMICS

2.A. Communication between cell compartments in tissue

  • Primary and metastatic cancer microenvironment
  • Extracellular matrix
  • Basement membrane
  • The metastatic microenvironment
  • Pre-metastatic niche
  • Tissue communication and the cancer secretome
  • Cross-talk between different tumor entities
  • Vesicular and molecular secretory processes
  • Exosome signaling
  • Re-directing the flux of information in cancer microenvironment (i.e., anakoinosis)
  • Dysregulated metabolism in cancer tissue
  • Stress responses
  • Energy production
  • Authophagy
  • Redox control in cancer

2.B. Not only oncogenes: epithelial control of oncogene functions

  • Oncogene mutations in histologically normal tissues
  • Age- and tissue-dependent oncogene mutations in non-cancer context
  • Selective advantage of mutated oncogenes in non-cancer tissues
  • Oncogene mutated cells in healthy tissues behave as normal cells: not enough mutations, or tight anticancer tissue controls?
  • Viral carcinogenesis: when viral genes take control of cell and tissue homeostasis
  • Human vs. mice viral carcinogenesis
  • Viral oncogenesis can bypass cellular oncogene mutations
  • Carcinogenesis and the epithelial polarity
  • Role of microenvironment in control of oncogene mutated cells
  • Tissue control of oncogene functions as upstream tumor suppressor barrier
  • Tumor suppression by polarity genes
  • LKB1 controls the oncogenic functions of Myc
  • Polarity genes vs. classical tumor suppressors
  • More than just oncogene-induced apoptosis and oncogene-induced senescence

2.C. Therapy-induced alteration of communication between cell compartments in tissue

  • Post-therapy cancer repopulation
  • COX-2 and cancer repopulation
  • Genetic and micro-environment factors determining repopulation
  • Epithelial-to-mesenchymal transition
  • The genetic and epigenetic identity of cancer stem cells
  • DNA damage response (DDR)
  • Context-dependent pro- or anti-cancer role of DDR
  • Senescence associated secretory phenotype and the identity of senescent cells
  • Autophagy and tissue regeneration
  • Endoreduplication and neosis
  • Phoenix rising: when induced apoptosis projects post-therapy tissue regeneration
  • Apoptosis and tissue regeneration
  • Intersections between apoptotic and senescent cells secretomes
  • Metronomic therapies
  • Reprogramming of cancer tissue and immune response upon low pulsed dose chemotherapy
  • In vitro modelling of metronomic chemotherapy
  • Targeted therapy and cancer tissue remodeling

2.D. Epigenetic alterations and dysregulated homeostatic pathways and checkpoints in cancer

  • Dysregulated homeostatic pathways
    • Wnt pathway in cancer
    • Notch signaling
  • Modulation of transcription factors
    • STAT3 in tumor disease
  • Reprogramming by epigenetic modelling
    • Regulation of tumor suppressor PTEN
    • Tumor suppressor modulation
  • Regulation by non-coding RNAs

2.E. Novel technical approaches to study the principles of anakoinosis

  • New prospects in animal models for studying cancer
  • Real time analysis of cancer cells in mice
  • Zebrafish
  • High tech in vitro studies: 3D cultures
  • organoids
  • lab-on-chip
  • Projecting in vitro the cancer microenvironment
  • Co-culturing epithelial, stroma and immune infiltrates
  • Microfluidic models
  • Lessons from regenerative medicine
  • Mathematical modelling of cancer dynamics
  • Simulations of tumor cells growth and response to therapy
  • Analyses in vivo

SPECIAL LECTURE: CANCER AS A TISSUE DISEASE

SESSION 3

ANAKOINOSIS, A NOVEL LONG-LASTING OPPORTUNITY FOR SUSTAINABLE DRUG DEVELOPMENT

Introduction: Anakoinosis, or targeting the functional state of tumor tissues:

why we need drug development

3.A. Developing immunotherapy

  • Immunotherapy re-challenge
  • Immune modelling for improving efficacy of cancer therapy
  • Immunotherapeutic combination therapies

3.B. New bio-modulatory drugs

  • Transcriptional modulators
  • Agonists and antagonists of nuclear receptors
  • Non-coding RNA
  • Drug cocktail kits
  • Ongoing research
  • The renin angiotensin system
  • MEK inhibitor, PPARγ
  • Bcl2 inhibitors
  • Peroxisome proliferator-activated receptor γ (PPARγ)
  • Future prospective
  • Drug design
  • Bioinformatic approaches
  • Drug repurposing: Not only saving

3.C. Stabilization of natural compounds and endogenous modulators

  • Anticancer activity of natural compounds
  • Pro-apoptotic activity
  • Tumor microenvironment modulation
  • Conjugation and encapsulation of for stabilization and targeting
  • Non-coding RNA
  • Nanomedicine
  • Gold nanoparticles
  • Drug targeting: enhanced permeability and retention effect

Intrinsically active nanoparticles as regulators of cancer microenvironment