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