Tumor Evolution & Progression

Cellular injury is the major cause of sporadic cancers.

Cellular injury if stalled in the G1 phase causes the majority of sporadic, (adult), cancers.

What is the research problem

It is not known how when and where cancer starts.

How will your solution make a difference

Research conducted in the G1 phase will produce relevant results for adult cancers. A stalled G1 phase in a cellular injury is a precursor for premalignancy, which is a precursor for malignancy. The G1 phase inhibits p53 preventing apoptosis.

What is your proposed solution

Most sporadic, (adult) , cancer will start from a cellular injury. If for any number of reasons, the cell cycle becomes stalled in the G1 phase, the injury will turn chronic. A transient G1 phase is healthy, but with the exact same cellular settings, a stalled G1 phase will be toxic. Research for adult cancers must be conducted in the G1 phase condition. Present research is going nowhere because it is conducted in the wrong settings.

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Tumor Evolution & Progression

HERVs and cancer genes as therapeutic target

Cancer development involves independent genetic alterations of genes that regulate cell proliferation, differentiation, and survival. Chromosomal alteration is crucial to cancer progression. Thus, Targeting HERVs & cancer gene loci may be important

What is the research problem

Targeting Human endogenous retroviruses and cancer gene loci at a time.

How will your solution make a difference

Reversing unnecessary mutation

What is your proposed solution

Antibody against HERVs

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Tumor Evolution & Progression

Breast Cancer Linked to Cell Phones Stored in the Bra

Case Reports are accumulating of young women with no family history getting a diagnosis of breast cancer. Tumors were unusually located directly underneath the skin where patients placed cell phones in their bra. More data needs to be collected.

What is the research problem

Documentation is needed. Oncologists need to ask patients if they store their cell phone's in their bra. Watch Dr. Lisa Bailey, past President of the American Cancer Society CA call for such documentation. https://goo.gl/NtDk5J

How will your solution make a difference

Cell phones have instructions in manuals that they should NOT be in bras or pockets. They are to be at distance from the body to meet FCC regs. With data collection and education we will have more definitive data, and hopefully prevent cases.

What is your proposed solution

Research is critically needed: Development of a tool with basic interview questions that clinicians can ask to characterize exposures past and present. Systematic collection. A database to maintain the information. Outreach to clinicians with the tool. In addition, patients need education on ways to reduce exposure.
Read the published case studies on women with cell phone related breast cancer here.
http://goo.gl/rNZ6xJ

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Tumor Evolution & Progression

I'm Not Quite Dead Yet; Include Metastatic Disease Research

580,000 Americans die each year from cancer. The majority from metastatic cancer. We need to not write these patients off every year. Currently we are. We are leaving a half million Americans behind every year by excluding metastatic research.

What is the research problem

The majority of cancer deaths are from metastatic cancer. Sadly, only a very small portion of research dollars go towards studying metastatic disease. Even more crazy, we don't collect accurate data on when patients progress to metastatic disease.

How will your solution make a difference

How can we do accurate research if we don't start with accurate data? I want to help with research and am excluded often. Include me. Share the data! It's insane that my taxes help fund research and it's not shared. Collaboration is key.

What is your proposed solution

) Add date of metastatic diagnosis to the designated medical record set whether original diagnosis, recurrence, or progression.

  1. Implement broad changes to improve clinical trial accrual and outcomes: Better access to trials, release of preclinical data that might inform patients, timely results. More access to trial drugs through compassionate care.

  2. Increase metastatic specific funding and more collaboration in research through the NCI

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Tumor Evolution & Progression

TUMOR EVOLUTION IS ALSO NON-GENETIC AND NON-DARWINIAN

Cancer progression is assumed to be driven by somatic Darwinian evolution and there is a myopic focus on mutations. However, non-Darwinian, Lamarckian-like mechanisms also play a role which offers a wealth of lever points for molecular intervention.

What is the research problem

The rigid doctrine of selection of genetic mutations that drive cancer progression remains unquestioned but is challenged by an increasing number of observations related to non-genetic phenotype plasticity that allows cell to escape therapy.

How will your solution make a difference

Some non-cancer, non-toxic drugs can control plasticity. They could be used off-label for the long-envisioned conversion of cancer to a chronic disease because often is the failed killing of cancer cells by cytotoxic therapy that provoke progression.

What is your proposed solution

Despite growing evidence that mutations play a subordinate role there is a myopic focus on cancer genomes. This suppresses alternative concepts that involve Lamarckian-like reprogramming of cancer cells in tumor progression. A broad research program that focuses on all the non-genetic, non-Darwinian processes may expose new target opportunities for drugs that do not kill (hence are less toxic) but prevent progression, by controlling plasticity.

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Tumor Evolution & Progression

Cell Phones/ Brain Cancer and Tumor Promotion

Replicated research studies suggest that cell phone radiation can impact tumor progression. Adequate data needs to be routinely gathered by clinicians on patients cell/Wi-Fi use. Patients need to be educated on reducing exposure to promote recovery.

What is the research problem

Alexander Lerchl of Jacobs University, replicated research indicating that carcinogen-induced tumor rates were significantly higher when mice were exposed to electromagnetic fields such as those emitted from mobile phones. http://ehtrust.org

How will your solution make a difference

In addition researchers have found decreased survival of glioma patients after long term cell phone use.
http://goo.gl/EfipAo
Helping cancer patients decrease their cell phone/Wi-Fi could result in better prognosis and survival.
Go to ehtrust.org

What is your proposed solution

Research studies need to be designed so that: on intake an assessment of the patients cell phone and wireless device use is documented in a systematic way to characterize the patient's EMF exposure on diagnosis.

Then, with education, patients can learn how to use technology with significantly reduced exposures (i.e a corded landline and ethernet connected laptops and computers) which in turn, will promote their treatment and recovery.

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Tumor Evolution & Progression

Data about breast cancer recurrence will help patient care

Better prediction of breast cancer recurrence will help tailor patient care and improve overall health. A combination of genetic, metabolic, and microenviroment studies could yield a comprehensive panel of predictors.

What is the research problem

A significant percent of mastectomies later have locoregional recurrence of the cancer. Currently, the major risk factors are size of the primary tumor and number of positive axillary lymph nodes, but are not enough to accurately predict recurrence.

How will your solution make a difference

Using this panel, doctors can more confidently avoid unnecessary treatment in patients who are unlikely to recur, while more closely monitoring high-risk patients and recommending irradiation which can decrease recurrence and improve survival.

What is your proposed solution

Collect biopsies, serum, and blood samples from the breast vasculature of patients prior to mastectomy. Compare gene expression, metabolic profiles, and immunological changes in the tumor microenvironment between patients who later recur verses those who don’t. Assemble a panel of the most significant differences between the groups, which when combined could be accurate predictors of recurrence and affect frequency of patient monitoring and care.

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Tumor Evolution & Progression

DEAD CANCER CELLS PRODUCED BY THERAPY PROMOTE PROGRESSION

Every dead cancer cell sends signals to its neighbor cells that makes them resilient to drugs. This is one reason why targeted therapy is inherently limited. This collective cell population level response could be a target for a new class of drugs.

What is the research problem

Cancer therapy always leaves surviving cancer cells among the dead cells. But the latter stimulate the former to become more malignant cancer stem cells. This contributes to "WHAT DOES NOT KILL STRENGTHENS" - explaining why targeted therapy fails.

How will your solution make a difference

We found compounds that promote removal of dead cancer cells. They could help "blunt" the unwanted edge of the double-edge sword that potent cancer drugs are. Used in combination with new therapies would make them more precise and more effective.

What is your proposed solution

Because of the above, therapy is almost always a DOUBLE-EDGED SWORD, notably the new potent drugs. We must study the signals through which dead cancer cells generated by treatment promote recurrence. We need to remove the dead cell bodies quickly when treating cancer. A type of macrophages specialized in removing dead cells could be specifically stimulated during treatment. Sadly, NCI is not interested in debris-stimulated tumor progression.

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Tumor Evolution & Progression

Single mom MBC no one to care for kids after my demise. Help us!

The ideas presented in this research idea are aimed better understanding and treating metastatic cancer across all types of cancer.

What is the research problem

The vast majority of cancer patients die from metastatic disease. There is a dearth of funding that focuses on met research, as well as general information that could be systematically collected in order to help our understanding of metastasis

How will your solution make a difference

The ideas proposed here will help generate the data and knowledge that are needed in order to drive better therapies for people with metastatic cancer.

What is your proposed solution
  1. Add date of metastatic diagnosis to the designated medical record set whether original diagnosis, recurrence, or progression.

  2. Implement broad changes to improve clinical trial accrual and outcomes: Better access to trials, release of preclinical data that might inform patients, timely results. More access to trial drugs through compassionate care.

  3. Increase metastatic specific funding and more collaboration in research through the NCI

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Tumor Evolution & Progression

CURBING THE NEAR OBLIGATE RECURRENCE FOLLOWING ANY NEW THERAPY

All therapies seek to kill tumor cells. But killing is probabilistic. The inevitable surviving cancer cells are stressed to become cancer stem-cells. Therapy backfires in hidden ways. Targeting this cell response will improve existing therapies.

What is the research problem

Killing all tumor cells is near-impossible since tumors are heterogeneous and non-linear and therapy probabilistic: it kills cells but creates new cancer stem cells: WHAT DOES NOT KILL, STRENGTHENS. How can we suppress this intrinsic cell response?

How will your solution make a difference

Non-killing cancer cell reprogramming drugs exist among FDA-approved non-cancer drugs but have not been studied with the above rationale. Such non-cytoxic drugs could be deployed quickly and may boost all the new potent cell-killing therapies.

What is your proposed solution

We must avoid "strengthening" surviving cancer cells by attempts to kill them. New therapies all seek to kill cancer cells. Since cancer cells can be “reprogrammed” into a variety of states, we can steer them to alternative, non-malignant states without provoking generation of cancer stem cells. Straightforward assays can be designed to screen for non-cytotoxic "gentle" drugs that reprogram cancer cells while avoiding killing/stressing them.

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Tumor Evolution & Progression

Dual LOX/COX blockade for cancer prevention and treatment

Arachidonic acid is a key mediator of inflammation, which plays a role in carcinogenesis. Prostaglandins and leukotriene blockade may decrease the risk of premalignant transformation, influence cell survival and modify radiation response.

What is the research problem

Inflammation plays a role in carcinogenesis, NSAIDs may help reduce colon cancer risk but there may be more effective approaches. Many systemic therapies, radiation can induce inflammation. COX inhibition alone not effective for radiosensitization.

How will your solution make a difference
  1. Take advantage of already proven safe drugs as potential novel antineoplastic agents
  2. May help with reducing risk of carcinogenesis
  3. May amplify efficacy of radiation as radiosensitizer
  4. May modulate or lessen toxicity of radiation therapy
What is your proposed solution
  1. Investiagate combination 5-LOX inhibitor zileuton + selective COX inhibitors, as well as dual inhibitor licofelone, as potential approaches to risk reduction for colon cancer.
  2. Evaluate same candidate drugs in preclinical validated models as potential radiosensitizers
  3. Consider moving to clinical trials quickly since zileuton, licofelone already used for asthma and osteoarthritis, respectively

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Tumor Evolution & Progression

Increase research into what causes cancer to become metastatic

Increase funding and research focus into what causes cancer to become metastatic. Create NCI working group and SPOREs for metastatic cancer and research metastases across solid tumor types.

What is the research problem

Metastatic cancer is what causes most cancer deaths, yet relatively little research focuses on what makes cancer become metastatic. This issue affects all solid tumor types.

How will your solution make a difference

Identifying and understanding what makes a cancer become metastatic can lead to treatments that prevent early stage cancers from progressing, cancer prevention methods, and hopefully cures for metastatic cancers.

What is your proposed solution

Create an NCI working group for metastatic cancer. Create SPOREs for metastatic cancer research. Place more research funding and emphasis on what makes a cell able to leave its original microenvironment, invade neighboring tissue, travel through blood and lymph, and grow in a different environment.

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Tumor Evolution & Progression

Cure Cancers by Inhibiting Cell Death Reversal Through Anastasis

Cancer cells can reverse cell death process & harbor damaged DNA by undergoing anastasis(Greek:rising to life). We propose to cure cancer by targeting anastasis to prevent survival of the damaged cells responsible for cancer recurrence & progression.

What is the research problem

Although current cancer therapies can effectively kill primary tumor cells, relapse often occurs, in which the cancer cells acquire new mutations to resist the therapy. Thus, tumors evolve to become aggressive, leading to cancer treatment failure.

How will your solution make a difference

Apoptotic cell death is generally assumed to be irreversible. Overturning this dogma, we found that cancer cells can reverse the cell death process at the execution stage, and propose to cure cancers by targeting this unexpected recovery process.

What is your proposed solution

Dying cancer cells can recover from the brink of death. Some of these recovered cells can acquire new DNA mutations that resemble those found in aggressive, drug-resistant tumors. This reveals an unexpected tactic cancer cells could use to escape cancer therapy, and to develop drug resistance. We propose to suppress this post-therapy escape pathway of anastasis in cancer cells, thereby cure cancers by inhibiting tumor recurrence & progression.

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Tumor Evolution & Progression

Combining 2-DG and Fenofibrate Kills a Wide Variety of Cancers

Using a combination of 2-DG (2-Deoxy-D-glucose) and fenofibrate effectively exploits 2 universal cancer traits - increased glucose uptake and increased stress - to effectively target the entire tumor, paving the way for a universal cancer treatment.

What is the research problem

Chemotherapy attacks only the fast growing outer cells of a tumor, not the slow growing inner cells (which are the most metastatic), as well as killing healthy cells. Further, targeted therapies are unable to simultaneously attack the entire tumor.

How will your solution make a difference

This unique combination of 2-DG and fenofibrate delivers a non-toxic treatment that has so far been shown to be effective in a wide variety of human cancers. Our hope is to bring this non-toxic treatment to millions of cancer patients worldwide.

What is your proposed solution

2-DG (2-Deoxy-D-glucose), a simple sugar, has been shown to inhibit glycolysis, which the most malignant cancer cells found in the inner core of all solid cancers rely on to survive. Using a combination of 2-DG and fenofibrate (a compound that has been safely used in humans for over 40 years to lower cholesterol and triglycerides), we have proven that the entire tumor can effectively be targeted without the use of toxic chemotherapy.

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