Biomarkers Promote Anti-tumor Drug Development

Biomarkers are the most direct and rapid diagnostic tools. Their screening and acquisition can play an important role in disease diagnosis, development, treatment, and efficacy monitoring. It is also an important target for drug development.

Biomarker refers to a biochemical indicator that can objectively measure and evaluate changes or possible changes in system, organ, tissue, cell and subcellular structure or function. It has a very wide range of uses and can be used for disease diagnosis and judgment. Disease staging or evaluation of the safety and efficacy of new drugs or new therapies in the target population can also help researchers to propose more effective treatments, especially in chronic diseases such as cancer, cardiovascular disease, diabetes, and neurological disorders. It has important value in the prevention and control of complex diseases.

Biomarkers in Cancer

  1. Nat Med: Chinese scientists discover new prostate cancer biomarkersthat are expected to improve individualized therapy for cancer

In a study published in the international journal Nature Medicine, researchers from Fudan University and Mayo Clinic in China identified a new mechanism of prostate cancer resistance to therapy through joint research. The development of new prostate cancer therapies provide ideas and hopes. In the article, the researchers explained that the mutations in the SPOP gene play a key role in the drug resistance of prostate cancer. The SPOP gene mutation is the most frequent genetic mutation in primary prostate cancer. These mutations are in the cancer pair. BET inhibitor drugs play an important role in the development of tolerance.

  1. Cell-metabolism:A team of scientists in Australia recently discovered a new type of lung cancer biomarker. These cancers have also been found to produce specific metabolites that may be identified in plasma samples, thereby increasing the hope that diagnostic blood test methods for such diseases can be developed in the future.

Kate Sutherland, co-director of the study, said, “One-fifth of the lung adenocarcinomas have changed in the KEAP1 / NRF2 pathway, indicating that it is a major cancer driver. These cancers are very aggressive and resistant to standard therapies. Force and poor prognosis, so new treatments are urgently needed.”

Up to 40% of lung cancers are lung adenocarcinomas, and one in five of these specific tumors are resistant to chemotherapy and radiation. The new study suggests that these specific cancers may respond well to a new generation of anti-PD-1 and anti-CTLA-4 immunotherapies. The ability to easily and quickly identify these specific tumors will enable physicians to better identify those who respond best to new immunotherapy treatments.

Another result of this new study was the discovery of unique metabolic markers that can be found in blood samples, pointing out potential early detection blood tests. “We worked with our colleague Dr. David De Souza and Prof. Malcolm McConville of Bio21 to identify a unique ‘breadcrumb’ trace of these cancers in the blood,” Sutherland said. “We hope that this test will identify patients who may respond to immunotherapy, and may also be a simple non-invasive blood test that can detect these lung cancers early.”

This study currently only finds this molecular pathway in animal models, so the next stage is to validate these results in human lung samples. Since then, clinical applications may take some time to become a reality, but this finding is critical to creating blood tests that both diagnose lung cancer and guide doctors to the most likely successful treatment.

  1. Nature Communications:Researchers from the National Cancer Research Center (CNIO) in Spain have successfully identified biomarkers for breast cancerthat can be classified for the first time. This is the first time that a curable patient can be distinguished from a patient who may relapse. Open. It also identified new pharmacological indicators and indicated that combination therapy with existing drugs may be effective in patients with these indicators.

Specifically, they identified six protein kinases whose functional status predicts the evolution of triple-negative breast cancer. In addition, researchers have found a way to detect these proteins in hospitals, so in the future it may develop into a routine clinical trial, just like the genetic analysis of any tumor today.

From genomics to proteomics

Research on cancer genomics for decades has revealed dominant gene mutations in many cancers that determine tumor progression and guide the design of individualized therapeutic approaches. This type of specific treatment for each type of tumor is more effective than traditional chemotherapy and is a major cause of advances in cancer treatment in recent years.

However, triple-negative breast cancer is caused by a variety of mutations that work together in a unique combination of each patient. To date, no dominant gene mutations have been identified that provide prognostic indicators or drug treatment responses.

To achieve this goal, CNIO researchers chose not to analyze the genes involved in triple-negative breast cancer, but to analyze their products: synthesize proteins sorted by these genes. Their hypothesis is that many of the patient’s genetic changes can be translated into an identifiable pattern of functional status of all tumor proteins and their proteomes – activation or not.

The experimental results were very successful. In a tumor sample of 34 patients, the researchers discovered biochemical markers of tumor protein activation. Although the initial number of candidates exceeds two million, with the help of sophisticated bioinformatics tools, they found that among all these signals, accurate combinations can only be found in patients who have relapsed. These proteins are activated by kinases, which in turn are proteins, so the next step is to find the kinase responsible for this signal. Finally, the study identified six kinases that led to the formation of a proliferating pattern of proteomes in relapsed patients.

Six kinases indicate possible recurrence: We currently know that these six kinases play a key role in triple negative breast cancer. In this study, the authors validated the results of 170 patients and confirmed the value of these six kinases as markers. Patients who do not have these proteins activated have a 95% chance of being cured, or at least not relapsed 12 years after treatment. However, even if one of the six kinases is active, the risk of recurrence increases tenfold.

New clinical trials targeting kinase activation: Analysis of the functional status of proteins is not currently routinely tested in hospitals, but the authors have translated the activation pattern of kinases into immunohistochemical indicators that can be easily analyzed in hospitals. The goal is to determine whether these six kinases can be routine clinical trials, just like the genetic profiling of any tumor today.

Currently, researchers are focusing on other markers of disease, including standardized kinase diagnostic tests, and clinical trials of patients with advanced disease using the therapeutic combinations described herein.

  1. Int J Cancer:Colorectal cancer biomarkers–application of fecal microbes in the detection of colorectal cancer.

Colorectal Cancer (CRC) is the second leading cause of cancer death in the Western world. CRC In most cases, genomic mutations, such as the APC/wnt signaling pathway, induce cell proliferation, which in turn leads to adenoma formation. The gradual accumulation of a driver mutation eventually leads to the formation of invasive tumors. If the CRC can be diagnosed at an early stage, the five-year survival rate can reach 80% or more. If the tumor cells have metastasized in the advanced stage, the five-year survival rate is less than 10%. Therefore, if early screening can be done in various countries, the mortality rate of CRC can be reduced.

The current fecal occult blood test (FOBT) is the most widely used colon cancer screening method, but its sensitivity and specificity for CRC detection is not high; colonoscopy is currently the most effective method for diagnosing CRC, but the operation is complicated and the patient experience is poor. Previous studies have found that changes in the intestinal flora are associated with CRC, but the potential of microbes as markers for colorectal cancer screening has not been clearly elucidated.

Therefore, researchers from Sweden used a nested case-control study to investigate the use of three microbial markers in fecal clBA + bacteria, afa-C+ diffuse E. coli, and Fusobacterium nucleatum in 238 subjects. The case of potential screening markers for CRC diagnosis.

The researchers found that clBA+ bacteria and individual markers of Fusobacterium nucleatum were more abundant in the stool of colorectal cancer patients and had higher specificity in predicting cancer (81.5% and 76.9%, respectively), and their sensitivity. They were 56.4% and 69.2%, respectively. In a combined trial of clBA+ bacteria and Fusobacterium nucleatum, the specificity of CRC diagnosis was 63.1% and the sensitivity was 84.6%.

The findings of this study support the ability of microbes in feces to serve as potential non-invasive biomarkers for CRC detection, and the method has potential value. The researchers suggest that, in the future, microbial markers may be an important screening strategy for patients with CRC who have “high risk” for other diagnostic methods such as colonoscopy.

Reference:

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