Stageing a různé typy pokročilosti

Castration-resistant PCa (CRPC)

• Cca 21% of men with CRPC have genetic somatic alterations [5]

AR-V7

• Ligand-independent splicing variant AR-V7 [9]
• Constitutively active AR variant V7 (AR-V7) [9]
• AR-V7 was found in 39% of bone metastases
• Consistently coexpressed with FASN
• In patients treated with enzalutamide and/or abiraterone FASN/AR-V7 double-positive metastases were found in 77% of cases
• Rationale for the use of FASN inhibitors in mCRPCs, including those overexpressing AR-V7 [9]
• AR-V7 lacks the C-terminal ligand-binding domain of full-length AR (AR-FL)
• Functions as a constitutively active
• Ligand-independent transcription factor
• Drives growth of mCRPC cells in vitro and in vivo
• AR-V7 mRNA and protein are
• Up-regulated in mCRPC bone metastases
• Associated with a decrease in overall survival
• Resistance to Enza and/or Abi treatment [9]

Localised prostatic cancer

• Cca 10% of patients with localized PC harbor germline mutations
• There might be an association with intraductal/ductal pathology [5]

Metastatic prostate cancer (mPCa)

• 150 metastatic site biopsies
• 12.7% BRCA2
• 5.6% ATM
• 0.7% BRCA1 [4]

Gradeing

Gleason system to grade prostate tumors

• Gleason score 2 to 10
• 10 indicates the most abnormalities
• Pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope
• Then does the same for the second-most-common pattern
• The sum of these two numbers is the Gleason score [11]

Whitmore-Jewett stage

• Another method sometimes used [11]

Invaze

• May invade rectum, bladder and lower ureters after local progression [11]

Metastázy

• The cancer cells may spread from the prostate
• Bones
• Lymph nodes [11]

Prostatic cancer

• Cca 11.8% of metastatic PC patients have germline mutations [5]

TNM system

• Clinical T1 and T2 cancers
• Only in the prostate
• T3 and T4
• Spread elsewhere