Clinical Trials for TP53 Wild Type Tumors

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What is the TP53 Mutation?

Clinical Trials for TP53 Wild Type Tumors: TP53 is dysregulated in a majority of human solid and hematological tumors. TP53 directly or indirectly regulates multiple cellular functions including cell cycle, apoptosis, DNA repair, and cellular senescence. TP53 dysregulation can generally be attributed to two factors:

  • Somatic or germline mutations of TP53
  • Excessive negative regulation of wild type TP53 by MDM2/MDM4 genes

What is the TP53 Mutation?

Over 50% of tumors have mutations in TP53 which leads to the loss of tumor suppressor function of the protein leaving the cell more vulnerable to physiological stresses leading to tumorigenesis. Several pharmaceutical companies are investigating small molecules that restore the function of TP53 to overcome loss of function mutations; these clinical trials are in early stage and are awaiting convincing clinical results.

What are the Clinical Trials for TP53 Wild Type Tumors?

In tumors where TP53 function is wild type and intact, the primary mechanism of downregulating wild type TP53 is by over expression of its negative regulators MDM2 and MDM4. MDM2-TP3 interaction prevents wild type TP53 from binding to targets that promotes tumor suppression. Additionally, MDM2 and MDM4 work together to tag wild type functional

TP53 for removal from the nucleus of the cell and promote degradation in the proteasome. MDM2 and MDM4 amplification in general is seen in about 2-7% of cancers and are usually mutually exclusive of TP53 mutations. In certain subtypes of sarcoma, the incidence of MDM2 amplification can be over 20%.

Currently multiple compounds inhibiting the interaction between TP53 and MDM2/MDM4 are in clinical evaluation in TP53 wild type tumors. MDM2 inhibitors currently in clinical trials for tumors with wild type TP53 include Idasanutlin, RG7112, AMG232, HDM 201, DS-3032b, CGM 097, ALRN-6924. Reactivation of the TP53 pathway via inhibiting the MDM2/MDM4 axis is particularly compelling for treating hematological malignancies that show low levels of TP53 mutations.

These clinical trials may also benefit from a combinatorial strategy with chemotherapy or immunotherapy. One example of a clinical trial that uses MDM2 inhibitors for TP53 wild tumors is the TAPISTRY trial.

Myelofibrosis Symptoms

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Myelofibrosis Symptoms

How to understand Myelofibrosis Symptoms? Myelofibrosis is an uncommon type of bone marrow cancer that disrupts your body's normal production of blood cells. This disease occurs when bone marrow stem cells develop mutations in their DNA and affects approximately 1.5 cases per 100,000 people. The end outcome is usually an overproduction of blood cells from a malfunctioning spleen or a lack of red blood cells, which causes anemia. Patients may identify a range of myelofibrosis symptoms, from mild to severe, as a result of the normally spongy bone marrow becoming thick and scarred.

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Multicentric Castleman Disease Clinical Trials

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The Multicentric Castleman Disease Clinical Trials

Castleman disease (CD) is a rare disease of the lymph nodes and related tissues. Though CD is not officially a cancer, it behaves much like lymphoma. Multicentric Castleman disease clinical trials are focused on how to better detect and better treat this disease, so more patients have positive outcomes.

Multicentric Castleman disease clinical trials are responsible for all the current treatments for multicentric CD and are the only hope of developing new, more effective treatments with less side effects. CD is rare, so every chance to understand the disease’s process is important.

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What is tumor profiling, and do I need it?

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What tumor profiling 1

Absolutely! Molecular profiling reveals the tumor’s behavior, give us clues on any weaknesses, and the best drugs that can target those weaknesses. But not all tumor profiling is the same, and different vendors can give very different reports. Massive Bio helps you keep them in check.

Smoking and Cancer

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Cancer 2nd Opinion

Smoking increases mortality rates by 40% in people who smoke fewer than 10 cigarettes daily, by 70% in people who smoke 10-19 per day, by ninety percent in people who smoke 20-39 per day, and by 120% in people smoking two packs or daily. Research from the Canadian Lung Association found that smoking kills between 40,000 – 45,000, over the number of deaths caused accidental poisoning, AIDS, murder, fires, by traffic injuries and suicide. 50% of smokers may die of illness. Tobacco related diseases kill almost 438,000 United States taxpayers per year or 1,200 per day, making it the major cause of preventable death in the U.S. Read more “Smoking and Cancer”

We Put You First

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We know that you have many difficulties after being diagnosed with cancer 2nd opinion. We have various resources to support your fight against cancer.

We provide resources to explore different treatment options, clinical trial access and understand the latest therapies.

We review your case and provide a list of options from the more than 30,000 available clinical trials around the world.