Prostate Cancer
Prostate cancer begins when cells in the prostate gland start to grow out of control. The prostate is a gland found only in males. It makes some of the fluid that is part of semen. Almost all prostate cancers are adenocarcinomas. These cancers develop from the gland cells (the cells that make the prostate fluid that is added to the semen).
Cause
The prostate is a walnut-sized gland located below the bladder and in front of the rectum. It surrounds the urethra and produces a substance that contributes to semen, the fluid that carries sperm from the testicles. Most cases of prostate cancer—99 percent—are adenocarcinomas, which develop when gland cells mutate and grow out of control, forming a tumor.
Risk Factors
✓ Age: Men over 40 are at a higher risk of developing prostate cancer. The risk continues to elevate as men age. Prostate cancer occurs primarily in older men, with 2/3 diagnoses coming in men over 65. The average age for diagnosis is 67. Prostate cancer is the leading cause of cancer-related deaths in men over 75. However, most men diagnosed with prostate cancer do not die from it.
✓ Diet: A diet high in fat increases the likelihood of developing prostate cancer. High-fat food intake is thought to increase the body’s production of testosterone, potentially promoting abnormal cell growth on the prostate gland.
✓ Ethnicity: African-American men have a higher risk of developing prostate cancer and are twice as likely to die from the condition in comparison to Caucasian men, while Japanese men have the lowest risk.
✓ Genetic History: The likelihood of developing prostate cancer is higher if it runs in your family (i.e. brother or father), a fact which suggests that there may be an inherited or genetic factor to the condition.
✓ High Testosterone Levels: Unusually high concentrations of testosterone cause prostate abnormalities and may contribute to an elevated risk of prostate cancer.
Insights
Prostate cancer is the most common cancer found only in men and the third most common non-skin cancer diagnosed in Americans. The American Cancer Society estimates that nearly 175,000 new cases of Prostate cancer will be diagnosed in the United States in 2019.
Prostate cancer is a vexing male cancer representing an unmet need for therapies that halt Prostate cancer progression and recurrence, especially in African American males (30% of all new cases of cancer and 15% of deaths from cancer during 2019). There are approximately 3.1M men currently living with Prostate cancer in the United States. Despite increased screening and a steady decline in the number of Prostate cancer deaths over the years, prostate cancer still is the second leading cause of cancer deaths among American men. About 30,000 men die from the disease each year. The death rate is twice as high for African American men than any other group.
Prostate Cancer is generally an indolent tumor initially after first line androgen-deprivation therapy (ADT), but often exhibits widespread recurrence 5-10 years post ADT therapy (85%). Targeting the transition from organ-confined Prostate cancer (95% survival) to invasive and metastatic cancer (30% survival) is paramount to influencing Prostate cancer lethality. Current concepts of the basis for Prostate cancer transition from indolent disease, to aggressive cancer phenotype that escapes from the capsule and metastases includes a significant role for inflammatory signaling pathways.
ALT-100 Benefits
Aqualung Therapeutics is targeting nicotinamide phosphoribosyltransferase (NAMPT)), a novel damage-associated molecular pattern protein (DAMP), as a therapeutic strategy to reduce prostate cancer progression, metastases and lethality. Aqualung is also pursuing NAMPT for use as a possible diagnostic and prognostic tool for detection of prostate cancer (PCa) risk and severity. Based on our compelling preliminary studies, we hypothesize that NAMPT participates in tumor/host cross-talk to influence the microenvironment resulting in prostate cancer invasion and metastasis. Aqualung Therapeutics is targeting secreted extracellular NAMPT, (eNAMPT), as a novel and highly attractive target in prostate cancer. This strategy is in sync with the increasing appreciation of the role of inflammation in the progression to aggressive ADT-resistant, invasive prostate cancer. Based upon our preliminary data, we conclude that plasma eNAMPT levels detect aggressive prostate cancer earlier than PSA levels.
In summary, Aqualung has developed a humanized eNAMPT-neutralizing therapeutic (mAb), ALT-100 as a biologic therapeutic for reducing systemic inflammation and inhibiting activation of evolutionarily-conserved inflammatory cascades that we believe to drive Prostate cancer progression. We speculate that ALT-100 will antagonize the switch to aggressive ADT-resistant disease and preventing lethal prostate cancer. In addition, Aqualung is also developing novel eNAMPT-based companion diagnostic and prognostic biomarker/genotyping platforms for detection of prostate cancer risk and severity.