PCF’s P²rovocative Questions: Future RFAs

 
    1. What are the clonal survival mechanisms of hyperconcentrated nuclear AR in mPCA LRHR, Abiraterone, MDV3100 Resistant disease at patient relapse?
    2. How does the androgen receptor signal in the absence of androgen?
    3. What is therapeutically actionable against PIK3<->AR “dual negative reciprocal feedback” in mPCA patients?
    4. What mechanism causes “closed circle-daisy chains” of chromosomal fusions in men with lethal prostate cancers?  (Movember + Berger et al. Nature 2011)
    5. What are the primary resistance mechanisms and the attendant predictive diagnostics  for each of our FDA newly approved agents for mPCA?
    6. What is the mechanism of action of bone metastasis delivered α particle Rad223 that increases mPCA patient survival, and can Rad223 be combined, sequenced, and moved earlier  in patient treatment with micrometastatic osseous metastases?
    7. What is the mechanism of survival improvement with infusions of autologous 55% CD54+cells + recombinant fusion protein GMCSF+PAP in patient haemotopoeitic systems that increase survival without affecting tumor burden?
    8. What are optimum host immunotherapy manipulations for patients with mPCA prostate cancer?
    9. What are the population’s frequency rates of clonotypes at diagnosis and relapse?  Do they explain, in part, the disproportionate burden of PCA in African Americans and those with increase risk from family history?

body scan before and after treatment

  1. What are the mechanisms of bone pain resolution and vanished 99 Tc uptake with “HGF-1-cMET-ness-multiple kinase inhibitor” treatment?
  2. What clonal survival targets are we missing  that are discoverable  in longitudinal CTC interrogations and at rapid autopsy?
  3. Small and DeBono JCO “anti-dallying” question: based on newly approved therapies, how do we scientifically combine and sequence treatments then move them up early into patients with lower metastatic tumor burdens?
  4. Are there additional clonotypes of pca yet undiscovered that predict clinical behavior, sensitivity and resistance to existing experimental andFDA approved agents?
  5. What initiates chromosomal fusions and epigenomic changes, and how can they be prevented in the 20-40 year old prostate?
  6. What are the actionable control points for the micro-environment,e.g., RANK-L, Src for progression of lethal clones?
  7. What is the molecular physiology of obesity and energy balance on the signal transduction involved in progression of lethal prostate cancers in patients?
  8. What are the metabolic determinants from exercise that confer a rx survival advantage in men with prostate cancer?
  9. What are the inflammatory “H. Pylori” equivalent microrganisms within the prostate microbiota whose infection in the 20-40 year old prostate drive carcinogenesis?

 

Terms to know from this article:

Abiraterone

Zitaga Abiraterone is an oral medication that blocks the synthesis of androgens (male hormones), such as testosterone, inside the tumor. Abiraterone is FDA approved for the treatment of patients with metastatic castrate resistant prostate cancer.

androgen

A type of hormone that promotes the development and maintenance of male sex characteristics.

Metastasis

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a "metastatic tumor" or a "metastasis." The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-ta-seez).

Immunotherapy

Immunotherapy is a type of treatment that boosts or restores the immune system to fight cancer, infections and other diseases. There a several different agents used for immunotherapy; Provenge is one example.

Progression

Increase in the size of a tumor or spread of cancer in the body.

Tumor

A mass of excess tissue that results from abnormal cell division. Tumors perform no useful body function. They may be benign (not cancerous) or malignant (cancerous).

PCa

Abbreviation for prostate cancer; CaP is also used.