Disease of cellular proliferation characterized by uncontrolled cellular proliferation, local tissue invasion, and disseminated metastasis

Cancer is a disease condition characterized by uncontrolled proliferation of abnormal cells that grow into a tumor distinct from its surrounding tissue. Tumors may be benign, in which they do not escape their local context, or malignant, in which tissue boundaries are disrupted and invaded. Malignant disease is associated with metastatic spread, in which a tumor disseminates to distant tissues, and significant patient mortality.

Cancer is a genetic disease that can begin with a single mutation in a single cell. Due to exposure to environmental stressors, such as fine particle pollution, or endogenous stressors, such as aging-associated chronic inflammation, each cell's genome is exposed to potentially mutagenic events, in which the underlying DNA sequence is subject to change and/or degradation. The majority of these mutations will be a) in an inconsequential site of the genome, b) repaired by endogenous DNA repair effectors, or c) lethal to the cell in which they occur. However, in some events, the mutation may not be repaired, not lethal, and occur in a key gene regulating normal cell proliferation, such as p53 or epidermal growth factor receptor (EGFR). When these conditions are met, cancer may occur.

In normal tissues, cell proliferation is tightly regulated by multiple nested layers of feedback and control that either a) prevent a cell from dividing at the inappropriate time or b) rapidly kill off a cell that is trying to divide at the inappropriate time. These layers of proliferation control include cell-intrinsic genetic, epigenetic, and transcriptional factors as well as cell-extrinsic interactions with other cells, such as surveilling immune cells. In order to become a pathological condition, the initiating cancer cell must successfully evade all layers of control above. In order to be lethal, the cancer must then evade all pharmacological treatment, such as ionizing radiation and cytotoxic chemotherapy, in the clinic.

As an initiating cancer cell grows into a clinically-noticeable tumor, it must successfully surmount challenges to survival from the surrounding stromal tissue, immune surveillance, and loss of nutrient supply via tissue disruption. As it does so, a cancer tends to accumulate additional mutations (fostered by reduced "quality control" for DNA replication in rapidly-dividing cancer cells). The majority of these mutations will confer no additional tumorigenicity to a given cancer and are termed "passenger mutations". A minority of mutations will increase the malignancy of a given cancer and are termed "driver mutations" because they increase the relative fitness of the cancer cells in which they appear. Because cancer growth is constrained by tissue architecture, nutrient supply, and immune surveillance, cancer cells compete with one another for survival and access to the resources needed for proliferation. In this manner, an evolutionary pressure is induced such that cancer cell descendants, or "clones", that carry more driver mutations will out-compete their less-fit brethren and spread faster. Immune activity and clinical treatment introduce further evolutionary pressures on malignant cancers, which in turn drives the emergence of cancer phenotypes that suppress immune activation, favor metastasis, and enable treatment resistance.

As cancer emerges from the unique genetic background of each patient that it afflicts, it is a highly heterogeneous disease. While the cancers of the same tissue may exhibit broadly similar pathological characteristics, such the desmoplastic derangement common to most pancreatic ductal adenocarcinomas, there is significant genetic diversity between patients and even within a given tumor, driven both by the genetic background of the patient and the evolutionary competition for driver mutations mentioned above. It is due to these differences that a "cure for cancer" has been so elusive.

Treatment for cancer has historically relied upon the administration of toxic chemicals or radiation in the hopes that, because cancer cells are dividing more rapidly than non-cancerous cells, these toxic agents will prove more lethal in cancer cells than non-cancerous cells. In many patients and especially for early disease, this treatment is effective even if it causes potent side effects in other rapidly-dividing cell types, such as the immune system, gut epithelium, and hair follicles. However, as noted above, if treatment with toxic agents fails to eliminate all cancer cells, clones bearing driver mutations enabling the cancer cell to ignore the treatment mechanism of action may emerge, leading to treatment resistance which, in turn, drives all cancer mortality.

With the advent of cheap genetic sequencing, the field of oncology has begun shifting towards more-targeted treatment, in which a given patient's disease is molecularly profiled to rationally design a treatment regimen to which it is likely to be most sensitive. This has led to the development of cancer therapies that target specific mutations common in particular types of cancer, such as the ALK inhibitors in non-small cell lung cancer. This approach will continue to yield significant therapeutic benefit for common driver mutations, although there also exists a long tail of uncommon driver mutations that will prove more difficult to address in the clinic. These targeted approaches are still in the early phase in the clinic, but have led to substantial treatment success in previously intractable disease. Over time, continued development of molecularly-targeted therapies will lead to the accrual of a library of precision therapeutics from which oncologists can select individualized treatments that lead to pathological complete remissions in ever-greater numbers of patients.

Separately, the advent of high-resolution immune profiling has led to the discovery that the immune status of a given patient is a key determinant of cancer progression. In patients with highly active immune systems and no chronic inflammatory co-morbidities, an unrestrained immune system can keep an incipient tumor in check for many years or even completely eliminate it before it is noticed in the clinic. When the immune system fails to do so, these patients benefit from the use of targeted immunotherapies to inhibit tumor mechanisms of immune escape. However, the tumor microenvironment (TME) is a highly immunologically active site with multiple layers of interaction and feedback control in a stressed environment that antagonizes immune activation. Sustained TME factors can "reprogram" certain elements of the anti-cancer immune response, such as Th1 T-cells to regulatory T-cells, to become "immunosuppressive", leading to a disabled immune system unable to restrain disease progression. Across multiple types of cancer, the emergence of immunosuppressive signals portends worsened prognosis and increased patient death. To this end, the field of immuno-oncology is now developing myriad targeted therapies that alter the activation status of the immune system with the goal of alleviating immunosuppression and stymying further cancer growth. This, too, will ultimately lead to a broad library of targeted therapies from which immuno-oncologists can rationally design combination immunotherapies to re-activate a given patient's immune system and thus increase their response to treatment.




Further reading


Documentaries, videos and podcasts





Jacqueline Renfrow
August 19, 2020
Cancer does not take a break during a pandemic. Here's a patient experience about what it was like returning for treatment amid fears of contracting the virus.
Jessica Hamzelou
August 21, 2020
New Scientist
The microbes embedded in a tumour seem to influence how a person's cancer will develop and how well they will respond to treatment
Emma Yasinski
August 19, 2020
New Scientist
Some cancer cells spread through the lymphatic system where they can pick up a jacket of fatty acids that protect them against damage and let them travel further in the body
Press Trust of India
August 19, 2020
According to the statement, tobacco-related cancer is estimated to contribute 370,000 cases which is 27.1 per cent of the total cancer burden in 2020
August 11, 2020
New research suggests that although sociodemographic factors have been associated with poor outcomes for patients treated for testicular cancer, guideline-directed, expert care can help to address this issue. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). Numerous barriers to optimal treatment for testicular cancer exist in underserved populations, such as individuals from ethnic minorities and lower socioeconomic strata...
July 7, 2020
New research found that the likelihood of being diagnosed with advanced cancer decreased among individuals with low income after expansion of Medicaid coverage. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). The Affordable Care Act expanded Medicaid coverage for most adults in the United States with incomes up to 138% of the federal poverty level, and many states opted to do so starting in 2014. This led to increased enr...
By Jonathan Chadwick For Mailonline
July 1, 2020
Mail Online
Researchers in Australia found that olaparib, which is known by the brand name Lynparza, damaged the store of immature eggs in the ovaries of mice.
June 16, 2020
In the early days of the pandemic, patients and doctors were uncertain about how they would proceed with research -- but no one ever doubted that they would.
June 8, 2020
An educational video about hospice care can provide valuable information for patients with advanced cancer and their caregivers, improve perceptions of this quality form of care at the end of life, and increase its use. These are the findings of a study published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). Hospice delivers high-quality care to patients who are dying, and it typically uses less aggressive and less costly care at the end of life....
May 26, 2020
The diagnosis of cancer in a child can be devastating to parents and other loved ones, but in a recent study from Denmark, having a child with cancer did not appear to impact parents' risk of separation or divorce or affect future family planning. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). Childhood cancer can cause feelings of fear and uncertainty among parents and burden them with many practical challenges related...
Amirah Al Idrus
May 22, 2020
Syndax's lead cancer drug failed a phase 3 study in metastatic breast cancer, leading the company to abandon an FDA filing in that indication. The phase 3 study found that adding entinostat to hormone therapy did not help patients with HR-positive, HER2-negative breast cancer live longer compared to the hormone therapy alone.
April 22, 2020
In an analysis that included information on adults diagnosed with colorectal cancer between 40 and 49 years of age, almost all patients could have been diagnosed earlier if they had been screened according to current family history-based screening guidelines. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). In many countries, colorectal cancer rates are rising in adults under 50 years of age. To identify those at risk, cur...
April 6, 2020
Consuming a diet high in fiber was linked with a reduced incidence of breast cancer in an analysis of all relevant prospective studies. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). Because studies have generated inconsistent results regarding the potential relationship between fiber intake and breast cancer, Maryam Farvid, PhD, of the Harvard T.H. Chan School of Public Health, and her colleagues searched for all releva...
Stuart Clark
March 29, 2020
the Guardian
The constellation Cancer, with the beehive cluster, is high in the sky and well-placed for observation
Henry Bodkin
March 22, 2020
The Telegraph
National Health Service insist limited care for cancer patients is 'unlikely scenario'
March 12, 2020
New research reveals bias and stereotyping among clinical and research professionals who recruit patients to enroll in cancer clinical trials. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). It is important to include diverse patients in clinical trials to ensure that the results will apply to patients in the general population. Unfortunately, the proportion of racial and ethnic minorities participating in cancer clinical...
By Ian Randall For Mailonline
March 11, 2020
Mail Online
Scientists from Scotland have, for the first time, been able to measure exactly how much force these drills apply by creating their own 'cancer cells' in the lab.
February 27, 2020
Leap Day may exist to ensure that the calendar stays in line with the Earth's movement around the Sun, but it also gives us one more day in the year to share in new and exciting experiences. Through Leap Day, Mastercard has curated an array of Priceless Experiences across sports, entertainment, and travel, among others, to help consumers use that extra day to share their passions with someone they love. The experiences are now available for auction on . Mastercard...
February 10, 2020
New research indicates that a single dose of the human papillomavirus (HPV) vaccine is as effective as multiple doses for preventing preinvasive cervical disease, which can later develop into cervical cancer. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS). HPV is the most common sexually transmitted infection in the United States, and persistent infection with certain types of the virus can cause cervical cancer. To preve...
February 5, 2020
An International Journal of Cancer study that examined lung cancer rates in young adults in 40 countries across five continents uncovered a trend of higher lung cancer rates in women compared with men in recent years. The emerging trend was widespread, affecting countries across varied geographic locations and income levels. The changes appeared to be driven by a rising rate of adenocarcinoma lung cancer among women. Historically, lung cancer rates have been higher among men than wo...
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