Tumor Evolution & Progression

Molecular basis for cancer prevention

All "premalignant" lesions need to be characterized with regard to DNA sequence, RNAseq, proteomics, lipidomics, miRNA ect to fully understand a basis for preventing the progression of these early disease states

What is the research problem

Omic characterization of all premalignant and early cancer lesions before they become malignant

How will your solution make a difference

This will identify new targets for prevention of cancer and allow us to intercept the cancer process very early in its progression.

What is your proposed solution

Build an open database that contains all this information and can be accessed by all researchers world-wide

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Tumor Evolution & Progression

Field effect and promoter hypermethylation

"Field-effect" and its importance in cancer has been proposed in the 50's. Hypermethylation can silence some tumor suppressor genes while cause some genes to overexpress.

What is the research problem

Early cancer detection at a molecular level not when lesions are observed

How will your solution make a difference

Detecting cancer way early when molecular changes occur.

What is your proposed solution

An objective study on the biology (not epidemiology study) of Inflammation and anti-inflammatory pathway genes influenced by field effect at promoter level will advance our understanding and strategies to slow or even thwart cancer progression.

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Tumor Evolution & Progression

Include metastasis research as a moonshot goal

Metastasis causes 90% of cancer deaths, but we atull know very little about the metastatic process and how to stop it. Research in this area is vital to saving lives.

What is the research problem

Very little research is done into the causes of and treatments for metastasis, despite metastasis being the cause of 90% of cancer deaths. As a result, we still know very little about how metastasis happens and how to stop it.

How will your solution make a difference

Since so many deaths are caused by metastasis, across organ of origin, developing treatments to stop metastasis will dramatically decrease the death rate from cancer.

What is your proposed solution

Shift federal funding from research into treatment of early stage disease to research on metastasis.

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Tumor Evolution & Progression

More research needed into less common breast cancer

Cancer arising from lobules of the breast vs ducts accounts for 10% of all breast cx. Invasive lobular carcinoma is extremely hard to detect via palpating/imaging. Dense breast tissue makes it even harder to find. Yet little research is being done.

What is the research problem

Not enough attention is being paid to cancer that arises in the breast lobules versus the ducts. This cancer behaves very differently and can be more deadly because it is difficult to detect.

How will your solution make a difference

Research into lobular carcinoma will help better detect and target treatment for these tumors, which effect at least 10% of all breast cancer patients.

What is your proposed solution

Develop new ways of detecting lobular carcinoma beyond traditional imaging and monthly self exams, which are far less effective for detecting this kind of cancer in early stages. Characteristics of this kind of tumor should be evaluated independently of ductal carcinoma.

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Tumor Evolution & Progression

Fund Technology Advancements for Immagin NuclearEnzyme Activity

I feel funding advancements for "In-Cell" Imaging would be wise. For example, a lot information into tumorigenesis may be obtained if we were able to differentially image Histone acetylases/deacetylase activity within intact tissue.

What is the research problem

There is a literature gap with regard to epigenetic regulation of acetylases. The significance of certain studies which use dominant negative mutant proteins can be more fully appreciated in light of quantitating spatial enzyme activity.

What is your proposed solution

Provide funding for the above stated innovations.

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Tumor Evolution & Progression

Blood Biopsy Imperative

Amassing blood biopsies of patients with cancer and finding genetic correlates of heme and tumor genomes to response would be useful.

 

A large scale study would yield important data, but must be paired with powerful tools of analysis.

What is the research problem

The genetic component/mechanism of cancer progression and response to treatment is poorly understood.

How will your solution make a difference

Knowledge is power, friends, especially knowledge that may yield insight into mechanism.

What is your proposed solution

A blood biopsy imperative/ study across histologies with analysis between histologies to uncover more secrets.

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Tumor Evolution & Progression

CRISPR/Cas9 and Immunotherapy to Destroy Cancer Cells and Tumors

CRISPS Case 9 and immunotherapy, separately, and, in combination therapy, could induce apoptosis, destroying cancer cells and tumors.

What is the research problem

The research problem is the inability to eliminate all cancer cells and tumors, due to tumor heterogeneity, and the evolution of genetic mutation, resulting in relapse, and poor outcomes.

How will your solution make a difference

If researchers use the CRISPR/Cas 9 editing system, immunotherapy, and nanotechnology, in combination, attacking and destroying tumor DNA in the nucleus of the cell, this combo therapy might induce apoptosis and eliminate all cancer cells and tumors.

What is your proposed solution

I recommend using CRISPR/Cas9 gene editing tool and immunotherapy to destroy cancer cells and tumors as well as correct genetic mutations.

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Tumor Evolution & Progression

Biochemical characterization of cancer patients in Nigeria

Limited data is available on the molecular and biochemical characteristics of common cancers in Nigeria compared to other blacks and races. The information obtained will help to understand tumor behavior and progression

What is the research problem

There is limited data on the molecular and biochemical characteristics of cancer patients living in Nigeria

How will your solution make a difference

it will help to understand tumor behavior and progression and provide better clinical management

What is your proposed solution

To collect samples of cancer patients in Nigeria and study them

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Tumor Evolution & Progression

The deadly minority

Unfortunately, in most patients, it is a minority of drug-resistant tumor cells that are present but not detected at diagnosis (or that evolve) that kill patients. No 'omics technology is good enough at single cell analysis to solve this problem.

What is the research problem

Tumors are heterogeneous, & the molecular signatures of the deadly, minority drug-resistant cells are below the noise in all omics approaches. Furthermore, there are multiple mechanisms of resistance to a given therapy.

How will your solution make a difference

Effective cocktails of combination chemotherapies could be devised and used at diagnosis, killing the majority and the minority tumor cell populations when the patient presents, before the tumor burden becomes unmanageable.

What is your proposed solution

Profile tumors (BOTH genomic and proteomics) not only before but also after the emergence of drug resistance (paired samples from the same patient), when the tumor population is dominated by resistant cells whose omic signatures can be detected above noise. Do this on a large scale, not in small R01s. Aggregate data across therapies. Identify combinations of therapies to kill all cells in a tumor before the tumor burden becomes unmanageable.

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Tumor Evolution & Progression

Identify the stem cell minority in malignant brain tumors

High grade gliomas are the deadliest brain tumors known. Despite a combination of surgery, radiation, and chemotherapy, most patients die within 2 years. We need to identify the stem cell minority and target them with advanced therapies.

What is the research problem

High grade gliomas are the deadliest brain tumors. There is currently no established method for identifying and specifically targeting progenitor cells believed to be responsible for tumor recurrence and progression.

How will your solution make a difference

We should be able to cure this deadly cancer in the next ten years. It will require a moonshot initiative, but it will save millions of lives and many years of productivity lost otherwise.

What is your proposed solution

Recent research in rats has shown that there are stem-like cells with positive CD15 staining. These cells may be the primary target, but further research is needed. Different from ordinary x-rays, ion radiation therapy can overcome the resistance and reduce the aggressive behavior of these cells. We will need a moonshot approach to bring ion therapy back to the U.S. and integrate it into new therapeutic approaches.

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Tumor Evolution & Progression

Reprogramming cancer cells into dormancy

The theory of dynamic cell attractors provides a theoretical framework for understanding how to reprogram ordinary cells into stem cells. Similarly, it can be used to engineer solutions to reprogramming cancer cells into non-proliferative states.

What is the research problem

Even cancers that respond well to initial therapy can resurface months or years later. This is evidence of a dormant state that cancer cells can enter. Reprogramming tumor cells into dormancy may be a less toxic and more effective treatment paradigm.

How will your solution make a difference

Cancer attractors provide a theoretical framework for understanding the complexity of tumor progression and response to therapy. Prioritizing this sort of work through targeted funding will accelerate its development and testing in clinical trials.

What is your proposed solution

Many experiments have shown that some cancer tissues (e.g. breast) can be reprogrammed to a normal state by signals from the tumor microenvironment. Work is already being done in the field of systems biology on understanding how to control and drive complex gene network models, e.g. from cancer attractors to dormant or non-damaging phenotypes. Devote resources to accelerate work in this area and translate it into treatment protocols and trials.

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Tumor Evolution & Progression

Modulation of mitochondria for prevention of cancer

Mitochondria is central to cancer progression & several drugs don't act on cancer cells with bad quality mitochondria. It has been reported that Cancer cell phenotype can be reversed by replacing mitochondria.

What is the research problem

Since mitochondria play a central role in cancer progression, correcting mitochondrial genome may prove to be beneficial tool for cancer treatment

How will your solution make a difference

The cancer cells will no longer be supported by the internal metabolic system. It will also help us tackle a major problem of drug effectiveness in cancer cells.

What is your proposed solution

Using CRISPER based tools or the mitochondrial replacement tools, the cancer phenotype may be altered.

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Tumor Evolution & Progression

Require pathology second opinion on rare cancers

Data and outcomes can be clouded by the fact that no one questions a diagnosis. Pathologists and oncologists can make mistakes. We need to prevent cancers from being treated inappropriately because no one thought reevaluate a diagnosis.

What is the research problem

Confirmation bias can prevent a misdiagnosis from being caught. In a rare or hard-to-treat cancer, little response/poor outcomes are expected & won't be questioned. There is no way to know if some poor results are actually inappropriate diagnosis.

How will your solution make a difference

However infrequent, a misdiagnosis provides incorrect data for research at best and costs someone their life at worst. This will help improve data and outcomes by minimizing improper diagnosis and, therefore, treatment of certain cancers.

What is your proposed solution

If a pathologist diagnosis a rare cancer, require a second opinion from an pathologist who is an expert in that cancer. Do not allow frozen slices for evaluation.

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Tumor Evolution & Progression

PTEN target + FDA approved mTOR Inhibitors + Tumor Evolution

A clinical trial using *currently FDA approved drugs* (Everolimus and Temsirolimus) targeting PTEN mutation to control the evolution of metastatic ER+ breast cancer is Urgently needed. See attached article for the basis for this trail.

What is the research problem
  1. A recently published scientific article (attached) mentions "Tumours are subject to the same rules of natural selection as any other living thing."

  2. There is no clinical trial to test this for ER+ metastatic breast cancer with PTEN mutation.

How will your solution make a difference

For patients who have not already failed treatment with Everolimus/Temsirolimus, this trial (if made available nationwide from the get-go) may immediately give hope to many met. ER+ breast cancer patients to control their cancer longer.

What is your proposed solution
  1. Create a trial for metastatic ER+ breast cancer patients with PTEN mutations.

  2. Use currently FDA approved drugs that target PTEN- i.e. Everolimus (EVR) and Temsirolimus (TEM).

  3. Treatment should be administered as described on page 3 of the attached article, in the 3rd-to-last paragraph ("Solomon and his colleagues plan...")

  4. Because EVR and TEM are available nationwide, make this trial also available nationwide from the get-go.

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