Prostate Cancer KnowledgeBase | Ki-67

Ki-67 is a protein found in cells that are actively growing and dividing (proliferating). Normal prostate cells proliferate slowly and do not produce, or ‘express,’ Ki-67. However, in prostate cancer cells that are actively proliferating, Ki-67 is expressed in large amounts. Prostate tumors that contain lots of cells expressing Ki-67 are generally more aggressive. Ki-67 overexpression also points to poorer prognosis and a higher chance of metastases and recurrence. Ki-67 is a prognostic biomarker in prostate cancer and its expression does not necessarily point to a specific treatment strategy.

Testing

The expression of Ki-67 can be determined in prostate tissue specimens by immunohistochemical staining. This process uses proteins called antibodies to label cells that express Ki-67. The number of positive Ki-67 cells can be determined manually or by using a computer program. Immunohistochemical results are typically reported as a percentage of tumor cells expressing Ki-67, with the values ranging from 0% to 100%. This percentage may be referred to as the proliferation index.

The test for Ki-67is not a screening test, therefore, your doctor may or may not recommend it. Some medical facilities may perform Ki-67 testing onsite or the tumor specimen may be sent out to a specialized lab.

Molecular explanation

The Ki-67 protein is closely linked to a process known as the cell cycle, which can be thought of as a series of changes that a single cell undergoes as it prepares to divide into two cells. Scientists divide the cell cycle into different phases. Ki-67 is not found in cells that are at rest (G0 phase) or in the earliest stages of the cell cycle (G1 phase). Ki-67expression begins at the end of the G1 phase and increases as cells begin to duplicate their DNA during the synthesis (S phase), until they divide into two cells. In prostate cancer tumors, abnormal Ki-67 expression is associated with higher Gleason scores and more aggressive cancers as well as higher rates of recurrence and metastases.

Other instances

In addition to prostate cancer, the prognostic potential of Ki-67 expression has been reported in breast, brain, bladder, and colon cancers.

Further reading

Prostate Cancer Molecular Model

There are no targeted treatments for Ki-67. It serves as a prognostic biomarker in prostate cancer and its expression does not necessarily point to a specific treatment strategy.

FDA-approved therapies

Currently, there are no FDA- approved treatments that target Ki-67.

Experimental therapies

A recent study suggested that taking vitamin D daily decreases the levels of Ki-67 expression in prostate tumors. Although this study did not directly show that the proliferation of the tumor cells was inhibited, it does hold some promise for prostate tumors that are rapidly growing and dividing. It is important to note that further studies are needed to validate these findings. Before beginning a daily vitamin D regimen, you should discuss it with your doctor.

Further reading

Prostate Cancer Molecular Model

Please note: Most of the trials listed below do not involve testing patients for particular genetic abnormalities found in their prostate cancers. Targeted therapies for prostate cancer are mostly in early stages of clinical testing.

LOCALIZED PROSTATE CANCER: RADIATION, SURGERY, DRUGS

TRIAL NAME TRIAL ID PHASE
LOCALIZED PROSTATE CANCER: RADIATION, SURGERY, DRUGS
Phase III Study of ProstAtak™ with Standard Radiation Therapy for Localized Prostate Cancer (PrTK03) NCT01436968 Phase III
Efficacy and Safety Study of TOOKAD® Soluble for Localised Prostate Cancer Compared to Active Surveillance (PCM301) NCT01310894 Phase III
Hypofractionated Stereotactic Body Radiotherapy for Localized Prostate Cancer NCT01059513 Phase II
High-Intensity Focused Ultrasound in Treating Patients with Localized Prostate Cancer NCT01194648 Phase II
MR Image-Guided Therapy in Prostate Cancer NCT01377753 Phase II
Stereotactic Body Radiotherapy (SBRT) with Concurrent Boost for Low- and Intermediate-Risk Prostate Cancer (Prostate SBRT) NCT01409473 Phase II
CyberKnife Radiosurgery for Localized Prostatic Carcinoma NCT01045148 Phase II
Study of OGX-011 (Antisense to Clusterin) Given Prior to Radical Prostatectomy in Patients with Localized Prostate Cancer NCT00138918 Phase II
Study of MDV3100 as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer NCT01547299 Phase II
A Neoadjuvant Study of Androgen Ablation Combined with Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer NCT01696877 Phase I/II
Hypofractionated Radiation Therapy for Localized Prostate Cancer NCT01677845 Phase I

METASTATIC PROSTATE CANCER: TARGETED THERAPIES

TRIAL NAME TRIAL ID PHASE
Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100 (COMET-1) NCT01605227 Phase III
Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men with Previously Treated Symptomatic Castration-Resistant Prostate Cancer (COMET-2) NCT01522443 Phase III
BKM120 (PI3K Inhibitor) in Metastatic Castration-Resistant Prostate Cancer NCT01385293 Phase II
Hsp90 Inhibitor STA-9090 in Treating Patients with Metastatic Hormone-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy NCT01270880 Phase II
OGX-427 in Metastatic Castrate-Resistant Prostate Cancer with Prostate-Specific Antigen Progression While Receiving Abiraterone NCT01681433 Phase II
Tivantinib in Treating Patients with Metastatic Prostate Cancer NCT01519414 Phase II
Dovitinib(TKI258) in Patients with Castration-Resistant Prostate Cancer NCT01741116 Phase II
Pilot Study of PLX3397 in Patients with Advanced Castration-Resistant Prostate Cancer (CRPC) NCT01499043 Phase II
Axitinib (Receptor Tyrosine Kinase Inhibitor) before Surgery in Treating Patients with High-Risk Prostate Cancer NCT01385059 Phase II
Trial of Cabozantinib (XL184) in Castrate-Resistant Prostate Cancer Metastatic to Bone NCT01428219 Phase II
Cabozantinib Plus Docetaxel and Prednisone for Advanced Prostate Cancer NCT01683994 Phase I
Cabozantinib in Treating Men with Hormone-Resistant Prostate Cancer NCT01703065 Not open yet
Cabozantinib-S-Malate in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer NCT01812668
A Phase II Study of Cabozantinib (XL184) Therapy in Castrate Resistant Prostate Cancer (CRPC) With Visceral Metastases NCT01834651 Phase II
Magnetic Resonance Imaging in Measuring the Effect of Cabozantinib on Bone Metastases in Patients With Castrate Resistant Prostate Cancer NCT01599793 Phase II
Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer NCT01630590 Phase II
Cabozantinib Plus Docetaxel and Prednisone for Advanced Prostate Cancer NCT01683994 Phase I
XL-184+Abiraterone in Post-Chemo CRPC NCT01574937 Phase I
BKM120 (PI3K inhibitor) in Metastatic Castration-resistant Prostate Cancer NCT01385293 Phase II
Hsp90 Inhibitor STA-9090 in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy NCT01270880 Phase II
OGX-427 in Metastatic Castrate-Resistant Prostate Cancer With Prostate-Specific Antigen Progression While Receiving Abiraterone NCT01681433 Phase II
Tivantinib in Treating Patients With Metastatic Prostate Cancer NCT01519414 Phase II
Dovitinib(TKI258) in Patients With Castration-resistant Prostate Cancer NCT01741116 Phase II
Pilot Study of PLX3397 in Patients With Advanced Castration-Resistant Prostate Cancer (CRPC) NCT01499043 Phase II
Axitinib (receptor tyrosine kinase inhibitor) Before Surgery in Treating Patients With High-Risk Prostate Cancer NCT01385059 Phase II
A Study of HSP90 Inhibitor AT13387 Alone or in Combination with Abiraterone Acetate NCT01685268 Phase I/II
Pazopanib (TK Inhibitor), Docetaxel, Prednisone Prostate mCRPC NCT01385228 Phase I/II
A Study of BIND-014 Given to Patients with Advanced or Metastatic Cancer NCT01300533 Phase I
Selumetinib and Cixutumumab in Treating Patients with Advanced Solid Malignancies NCT01061749 Phase I
Lapatinib and Paclitaxel in Treating Patients with Advanced Solid Tumors NCT00313599 Phase I
Temsirolimus and Vorinostat in Treating Patients with Metastatic Prostate Cancer NCT01174199 Phase I
XL-184 + Abiraterone in Post-Chemo CRPC NCT01574937 Phase I
Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients with Advanced Solid Tumors or Prostate or Kidney Cancer NCT01480154 Phase I
Phase I Trial of the Mammalian Target of Rapamycin (mTOR) Inhibitor Everolimus Plus Radiation Therapy (RT) for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients following Prostatectomy NCT01548807 Phase I
A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects with Advanced Solid Tumors or Lymphomas NCT01588678 Phase I
Safety and Efficacy Studies of Panobinostat and Bicalutamide in Patients with Recurrent Prostate Cancer after Castration NCT00878436 Phase I
A Phase I Study of MLN8237 (Aurora A Inhibitor) in Patients with Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen NCT01094288 Phase I
Phase I/Ib Dose-Escalation of Dinaciclib with Weekly Paclitaxel for Advanced Solid Tumor Malignancies & Assessment of MYC Oncogene Overexpression NCT01676753 Phase I
ABT-888/Veliparib (PARP Inhibitor) in Treating Patients with Malignant Solid Tumors That Did Not Respond to Previous Therapy NCT00892736 Phase I

METASTATIC PROSTATE CANCER: HORMONAL THERAPIES IN COMBINATION WITH TARGETED THERAPIES

TRIAL NAME TRIAL ID PHASE
AMG 386 and Abiraterone for Advanced Prostate Cancer NCT01553188 Phase II
Abiraterone Acetate with or without Veliparib in Treating Patients with Metastatic Prostate Cancer NCT01576172 Phase II
Abiraterone Acetate and Prednisone with or without Dasatinib in Treating Patients with Metastatic Hormone-Resistant Prostate Cancer NCT01685125 Phase II
Bicalutamide with or without Akt Inhibitor MK2206 in Treating Patients with Previously Treated Prostate Cancer NCT01251861 Phase II
Cabozantinib and Androgen Ablation in Patients with Androgen-Dependent Metastatic Prostate Cancer NCT01630590 Phase II
BKM120+Abiraterone Acetate for Metastatic CRPC NCT01741753 Phase I
XL-184+Abiraterone in Post-Chemo CRPC NCT01574937 Phase I
A Phase II Trial of MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer NCT01799278 Phase II

IMMUNOTHERAPY FOR PROSTATE CANCER

TRIAL NAME TRIAL ID PHASE
A Phase III Efficacy Study of a Recombinant Vaccinia Virus Vaccine to Treat Metastatic Prostate Cancer (Prospect) NCT01322490 Phase III
Sipuleucel-T, CT-011, and Cyclophosphamide for Advanced Prostate Cancer NCT01420965 Phase II
Concurrent Versus Sequential Treatment with Sipuleucel-T and Abiraterone in Men with Metastatic Castrate-Resistant Prostate Cancer (mCRPC) NCT01487863 Phase II
Ipilimumab + Androgen Deprivation Therapy in Prostate Cancer NCT01377389 Phase II
Neoadjuvant Ipilimumab in Prostate Cancer NCT01194271 Phase II
Combining Ipilimumab with Abiraterone Acetate Plus Prednisonein Chemotherapy and Immunotherapy-Naïve Patients with Progressive Metastatic Castration-Resistant Prostate Cancer NCT01688492 Phase I/II
Vaccine Therapy with PROSTVAC/TRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer NCT00450463 Phase II
Neoadjuvant Study of Androgen Ablation Combined with Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer NCT01696877 Phase I/II
Anti-OX40, Cyclophosphamide (CTX) and Radiation in Patients with Progressive Metastatic Prostate Cancer NCT01303705 Phase I
Sipuleucel-T With or Without Radiation Therapy in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer NCT01807065 Phase II (not open yet)
Trial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer NCT01817738 Phase I/II
Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer NCT01875250 Phase II
Enzalutamide With or Without Vaccine Therapy for Advanced Prostate Cancer NCT01867333 Phase II
Dendritic Cell Vaccination and Docetaxel for Patients With Prostate Cancer NCT01446731 Phase II
Biological Therapy With or Without Vaccine Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer NCT01881867 Phase II
Adoptive Transfer of Autologous T Cells Targeted to Prostate Specific Membrane Antigen (PSMA) for the Treatment of Castrate Metastatic Prostate Cancer (CMPC) NCT01140373 Phase II
Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer NCT01560923 Phase II
Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer NCT01498978 Phase II
Sipuleucel-T and Ipilimumab for Advanced Prostate Cancer NCT01832870 Phase II
Natural Killer Cells and Bortezomib to Treat Cancer NCT00720785 Phase I
Phase II PAP Plus GM-CSF Versus GM-CSF Alone for Non-metastatic Prostate Cancer NCT01341652 Phase II
Phase II Study of Adenovirus/PSA Vaccine in Men With Hormone – Refractory Prostate Cancer (APP22) NCT00583024 Phase II
Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21 NCT00583752 Phase II
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