Tumor Evolution & Progression

Cancer Research Ideas - Tumor Evolution & Progression (Archived)

Cancer genomics has yielded a greater understanding of the mutations that occur within cancer cells and their roles in tumor initiation and progression. Concurrent with an increased understanding of cancer genomics, a greater appreciation has developed for the enormous heterogeneity of cancer cells that evolve within a tumor, the metabolic changes in both the cancer cell and immune cells in the microenvironment, and the roles of the non-cancer cellular and molecular components of the tumor microenvironment that both support and suppress tumor progression.

The submission period for Tumor Evolution & Progression ideas ended on July 1. However, we encourage you to sign up for regular e-mail updates about the National Cancer Moonshot Initiative at the Cancer Moonshot Milestones web page.

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.

Submitted by (@david.hicks)

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

Submitted by (@elfarukpath11)

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.

Submitted by (@devradavis)

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.

Submitted by

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.

 

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

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.

Submitted by (@cancrumvincemus)

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.

Submitted by (@devradavis)

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.

Submitted by (@deeptimathur)

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.

Submitted by (@cancrumvincemus)

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.

Submitted by (@katevered)

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.

Submitted by (@cancrumvincemus)

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.

Submitted by (@subatomicdoc)

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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