Can Liquid Biopsies and Tumor Biomarkers Personalize Prostate Cancer Treatment?


“Experimental, minimally invasive ‘liquid biopsy’ blood tests might soon help to personalize prostate cancer treatment by predicting androgen resistance and survival benefits from particular treatments, researchers announced at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.

“Liquid biopsies detect circulating tumor cells (CTCs) or bits of tumor DNA (ctDNA). Not all tumors shed cells or DNA into a patient’s bloodstreams, but most do. And when they do, they can reveal a lot about themselves—including molecular signatures that can be targeted with specific treatments.

“Recent years have seen an explosion of candidate biomarkers for prostate cancer and other malignancies, including both liquid biopsies and tumor-sample gene panels. Most candidate biomarkers have been prognostic gene-mutation signatures that can estimate patient survival regardless of what treatment strategies are attempted. These prognostic tests can be useful for risk-stratifying patients who are participating in clinical studies, or in communicating prognosis to a patient and his loved ones.”

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Gene Mutation Signals Poor Prognosis for Pancreatic Tumors

“For patients with pancreatic neuroendocrine tumors, the presence of recently identified mutations in two key genes is a prognostic factor for poor outcome, researchers report.

” ‘We found loss of nuclear expression in about 23% of the tumors that we studied, and this loss of expression was associated with worse tumors from the outset,’ lead investigator Michelle Heayn, MD, a second-year pathology resident at the University of Pittsburgh Medical Center, told Medscape Medical News.

“Pancreatic tumors with neuroendocrine histology frequently respond to chemotherapy and have a more favorable prognosis than the more common pancreatic adenocarcinomas. However, the mutations are associated with worse disease-free and disease-specific survival.”

Inflammatory Marker Linked With Poor Prognosis in Melanoma

“A new study indicated that the measurement of levels of C-reactive protein (CRP) in the blood has been found to be an independent prognostic marker for survival in patients with melanoma. Patients with the most markedly increased levels of CRP were found to be at high risk for melanoma recurrence and death.

“ ‘We believe it is reasonable to include measurement of CRP in prospective investigations of outcomes of patients with melanoma, including in trials of systemic therapy,’ wrote Shenying Fang, MD, PhD, of the University of Texas MD Anderson Cancer Center, and colleagues in the Journal of Clinical Oncology. ‘Furthermore, although these data cannot determine whether interventions to reduce inflammation and/or CRP could benefit selected patients with melanoma, they do suggest that preclinical investigation of such interventions is justified.’

“This study is not the first to show a link between levels of CRP and cancer. Prior research has shown an association between CRP and lung and colorectal cancer, and a small study indicated that the marker may be prognostic in patients with early-stage melanoma.”

SNP (–617C>A) in ARE-Like Loci of the NRF2 Gene: A New Biomarker for Prognosis of Lung Adenocarcinoma in Japanese Non-Smoking Women

The transcription factor NRF2 plays a pivotal role in protecting normal cells from external toxic challenges and oxidative stress, whereas it can also endow cancer cells resistance to anticancer drugs. We aimed to investigate the single nucleotide polymorphisms in the NRF2 gene as a prognostic biomarker in lung cancer.

SNP homozygous (c.–617A/A) alleles in the NRF2 gene are associated with female non-smokers with adenocarcinoma and regarded as a prognostic biomarker for assessing overall survival of patients with lung adenocarcinoma.

Molecular Circuit Involving KLK4 Integrates Androgen and mTOR Signaling in Prostate Cancer

“All cancer lesions sustain alterations in signaling pathways, which are the drivers of disease initiation and progression. Study of altered signaling in cancer is thus important to develop more effective therapeutic regimens as well as better prognostic markers. In this study, we show that two of the most frequently altered signaling pathways in prostate cancer, the androgen receptor and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways, are dependent on kallikrein related peptidase 4 (KLK4), whose expression is highly prostate enriched. Our results suggest that KLK4 has a central role in prostate cancer survival and that KLK4 silencing may have significant therapeutic efficacy.”

Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

“Current prognostic indicators are imperfect predictors of outcome in men with clinically-localized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study.”

Vascular Endothelial Growth Factor (VEGF) Expression in Locally Advanced Prostate Cancer: Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 8610

Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer…”

C-X-C motif receptor 2, endostatin and proteinase-activated receptor 1 polymorphisms as prognostic factors in NSCLC

The purpose of present study was to evaluate germline polymorphisms of three potential therapy targets – proteinase-activated receptor 1 (PAR-1), endostatin, and C-X-C motif receptor 2 (CXCR-2) – as prognostic markers for disease free survival (DFS) and overall survival (OS) in surgically treated NSCLC patients.

The PAR-1 -14 Ivs A/A genotype was associated with advanced tumor stages with shorter median OS in squamous cell lung carcinoma. The CXCR-2 +1208 T/T genotype was associated with aggressive tumor biology  and shorter DFS and OS in NSCLC and especially in squamous cell lung carcinoma a negative predictor for DFS and OS. Genotyping of the CXCR-2 +1208 C>T polymorphism could be a useful tool to identify high-risk squamous cell lung carcinoma subgroups.

Plexxikon updates Zelboraf Phase 1 data on BRAF V600E mutation-positive melanoma

Plexxikon today announced that updated Phase 1 clinical data of Zelboraf (vemurafenib) were presented at the Society for Melanoma Research (SMR) 2012 Congress, held November 8-11 in Los Angeles, CA.