Advances and Challenges in Precision Medicine for Diagnosis and Treatment of Prostate Cancer

PROSTATE CANCER AFFECTS ABOUT 1.3 MILLION MEN globally and is the second most common male malignancy in the United States (US). Approximately 248,000 new cases and 34,000 deaths are expected in the US in 2021.

Prostate cancer is a chronic disease, and treatment approaches vary based on a variety of tumor and patient-specific characteristics. A “watch-and-wait” approach to treatment tends to be adopted upon diagnosis in the elderly, given the typically long latency period of this disease and the potential frailty of this patient population. However, progressive, ultimately invasive, the disease requires guideline-based therapeutic interventions based on the stage of the malignancy. Exhaustion of these approaches may lead to subsequent enrollment in clinical trials exploring novel therapies/treatment approaches.

There is no “one-size-fits-all” approach to the treatment of prostate cancer. Because response rates to therapies depend on numerous patient- and tumor-specific factors, there is a great unmet need for more novel interventions following treatment failure. Precision medicine is increasingly becoming a tool used to

  • Unravel the intricacies associated with malignant tumor growth
  • Predict the course of disease following treatment with specific therapies
  • Help elucidate appropriate, novel biological targets for novel therapies

What is precision medicine?

Precision medicine is an umbrella term used to describe a host of disease-specific genetic and protein-based diagnostic/prognostic tests. When collectively conducted on an appropriate liquid/ cell/tissue biopsy from a patient, such tests are expected to yield information that

  • Enables clinicians to identify appropriate treatment courses for their patients
  • Allows treatment approaches to be personalized, given that the biopsy sample provided for examination is specific to an individual patient
  • Provides clinicians with an additional degree of confidence that a chosen therapy, based on evidence in the published literature, will yield successful outcomes for the identified anomaly
  • Enables clinical investigators to further understand the disease and its course, allowing for the identification of novel molecular targets for the development of new therapies.

Ultimately, precision medicine helps clinicians make more accurate decisions about the diagnosis, treatment, and prognosis of the disease. Accordingly, to obtain an individual tumor’s unique “fingerprint”, precision “oncology” relies on information provided by collections of established biomarker tests, as well as new technologically-advanced tests to identify/assess novel genes or proteins of interest. Precision oncology has been adopted for many types of cancer, including those of the prostate, lung, and breast. As technology advances, clinicians and researchers anticipate that precision medicine tools may help to answer essential questions about cancers, including the following:

  • Who is most at risk for disease and in need of closer screening?
  • Who will have the best chance of improved outcomes with a given treatment strategy, such as surgery or radiation?
  • How do the treatments work, especially novel therapies?
  • Who should receive more aggressive treatments earlier in the course of disease?
  • Who is more likely to relapse on a particular therapy?

Answers to questions like these would help lower the healthcare costs associated with inaccurate diagnoses and unsuccessful courses of cancer therapies.

Precision medicine as a tool to facilitate successful prostate cancer outcomes

Precision medicine is based on the study of genomics and proteomics. Genomics is the study of the structure, function, evolution, mapping, and editing of genomes, or a complete set of genes. Proteomics is the study of the entire set of proteins expressed, or potentially expressed, by a genome, cell, tissue, or organism. As more precision medicine data are collected in patients with prostate cancer, researchers are examining ways to use this information to fight the malignancy. These data may be collected in multiple ways within a single-precision medicine assay.

Next-generation sequencing: Also called high-throughput sequencing, captures a large amount of genomic information about a specific patient’s prostate tumor.

Protein expression analyses: Researchers are identifying certain proteins within the tumor microenvironment that help tumors resist therapy or grow aggressively. Proteins relevant in the setting of prostate cancer include NRG1 and LAM67R.

Biomarker testing incorporated into a precision medicine: Several biomarker tests are now available for patients with prostate cancer, including blood and urine tests. Many research groups are examining approaches to identifying novel, tumor-specific biomarkers to aid with prostate cancer diagnosis and prognosis. Researchers are also examining noncoding RNA biomarkers and their potential ability to predict drug resistance.

Gene fusion identification and incorporation into precision medicine: Researchers have identified specific, recurrent gene fusions that may be associated with prostate cancer. For example, one research group discovered that, in some cases, ETS transcription factors fuse with TMPRSS2, a prostate-specific, androgen-responsive gene. Such discoveries may help researchers develop prognostic biomarker tests for inclusion in precision medicine assays, and may provide new targets for the development of novel therapies.

Challenges to implementing precision medicine in prostate cancer

Several challenges must be addressed to advance the field of precision medicine in prostate cancer. In a 2020 article in Nature Cancer, Mateo and colleagues stated, “The optimal use of genomics to guide clinical decision-making in prostate cancer is not well defined, and there are no current guidelines to inform the timing, type of tissue,or optimal set of clinically validated laboratory tests. With a growing number of agents being used off-label, the data reported have mostly been non-systematic.” The authors called for more standardized approaches to tissue collection and analysis, as well as information-sharing so data are not “siloed”. This would give researchers access to more tissues for molecular profiling by precision medicine, to obtain more unique and valuable information about prostate tumor behavior.

For therapy to be truly “personalized”, researchers must gain an in-depth understanding of how unique tumor attributes affect people of different backgrounds, including sex, age, race, comorbidities, and medical and family history. As those relationships become clearer, and precision medicine becomes more advanced and more widely available, we will truly have the opportunity for successful personalized outcomes.

Bibliography

American Cancer Society. Precision or personalized medicine. https://www.cancer.org/ treatment/treatments-and-side-effects/treatment-types/precision-medicine.html. Accessed August 25, 2021.

Malik A. A new era of prostate cancer precision medicine. Front Oncol. 2019;9:1263. doi: 10.3389/fonc.2019.01263.

Mateo J, et al. Accelerating precision medicine in metastatic prostate cancer. Nat Cancer. 2020;1(11):1041-1053. doi: 10.1038/s43018-020-00141-0.

Prostate Cancer Foundation. What is precision medicine? https://www.pcf.org/about- prostate-cancer/prostate-cancer-treatment/precision-therapies-prostate-cancer/. Accessed August 25, 2021.