title: Modulation of sensitivity and resistance to multikinase inhibitors by microenvironmental platelet factors in HCC.
abstract: BACKGROUND
  Response of a tumor to chemotherapy or multikinase inhibitor therapy has been traditionally thought to be a reflection of the sum of the characteristics of both the drug and of the tumor cell resistance mechanisms. More recently, there has been a growing awareness of the role of non-tumor factors-both cellular and humoral-in the tumor microenvironment that can increase or decrease the tumor cellular responses to the therapy. This article focuses on platelet factors in clinical HCC and experimental evidence that they provide growth stimulants that can antagonize the growth inhibitory effects of therapy.
  
  
  METHODS
  Review of the mechanisms of multikinase cancer growth inhibitors and of the role of platelets in providing growth factors that can antagonize their effects.
  
  
  CONCLUSIONS
  These new ideas and data show that the response of a tumor to multikinase inhibitors or chemotherapy may be strongly influenced by microenvironmental factors. Conversely, antagonists to these environmental factors, such as EGFR inhibitors and IGF1-R inhibitors, might be expected to augment the anti-tumor effect of both chemotherapy and multikinase inhibitors.
authors.affiliation: a Laboratory of Cellular Biology, National Institute for Digestive Diseases , IRCCS "Saverio de Bellis" , Via Turi 27, Castellana Grotte , BA 70013 , Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: D'Alessandro
authors.affiliation: a Laboratory of Cellular Biology, National Institute for Digestive Diseases , IRCCS "Saverio de Bellis" , Via Turi 27, Castellana Grotte , BA 70013 , Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Messa
authors.affiliation: a Laboratory of Cellular Biology, National Institute for Digestive Diseases , IRCCS "Saverio de Bellis" , Via Turi 27, Castellana Grotte , BA 70013 , Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Refolo
authors.affiliation: a Laboratory of Cellular Biology, National Institute for Digestive Diseases , IRCCS "Saverio de Bellis" , Via Turi 27, Castellana Grotte , BA 70013 , Italy.|b Visiting Professor, Program for Targeted Experimental Therapeutics, Izmir Biomedicine and Genome Center , Dokuz Eylul University , Izmir , Turkey.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Carr
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D000077157:Sorafenib; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib; D009536:Niacinamide; D000077157:Sorafenib
keywords: microenvironment; platelets; regorafenib; resistance; sorafenib