autologous transplantation for several cancer types, although the side effects are also more severe. the cell based immunotherapy in which the patients own natural killer cells(nk) and cytotoxic t-lymphocytes(ctl) are used has been in practice in japan since 1990. nk cells and ctls primarily kill the cancer cells when they are developed. this treatment is given together with the other modes of treatment such as surgery, radiotherapy or chemotherapy and called as autologous immune enhancement therapy (aiet). immune checkpoint therapy focuses on two "checkpoint" proteins, cytotoxic t-lymphocyte–associated antigen 4 (ctla-4) and programmed death 1 (pd-1). under normal conditions, the immune system utilizes checkpoint proteins as negative feedback mechanisms to return to homeostasis once pathogens have been cleared from the body. in tumor microenvironment, cancer cells can commandeer this physiological regulatory system to "put a brake" on the anti-cancer immune response and evade immune surveillance. 2018 nobel prize in medicine is awarded to dr. james allison of university of texas md anderson cancer center in u.s. and dr. tasuku honjo kyoto university in japan for their contributions in advance of pd-1 and ctla-4 immune checkpoint therapy. hormonal therapy main article: hormonal therapy (oncology) the growth of some cancers can be inhibited by providing or blocking certain hormones. common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. blocking estrogen or testosterone is often an important additional treatment. in certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial. although the side effects from hormone therapy vary depending on the type, patients' can experience symptoms such as hot flashes, nausea, and fatigue. angiogenesis inhibitors main article: angiogenesis inhibitor angiogenesis inhibitors prevent the extensive growth of blood vessels (angiogenesis) that tumors require to survive. some, such as bevacizumab, have been approved and are in clinical use. one of the main problems with anti-angiogenesis drugs is that many factors stimulate blood vessel growth in cells normal or cancerous. anti-angiogenesis drugs only target one factor, so the other factors continue to stimulate blood vessel growth. other problems include route of administration, maintenance of stability and activity and targeting at the tumor vasculature. exercise prescription main article: exercise prescription exercise prescription is becoming a mainstream adjunct treatment for cancer, based on studies which show that exercise (compared to no exercise) is associated with reduced recurrence rates, improved mortality outcomes, reduction of side effects from traditional cancer treatments. although it is uncertain whether improved outcomes with exercise are correlated or causative, the benefit-risk ratio of including exercise as part of cancer treatment is large, as exercise has further benefits (e.g. cardiovascular, mental health) without major risks, although there is a small risk of overuse injury if added too aggressively. exercise physiologists and exercise medicine specialists can assist oncologists and primary care practitioners with exercise prescription in cancer patients. walking is usually an excellent exercise option as an adjunct cancer treatment synthetic lethality synthetic lethality arises when a combination of deficiencies in the expression of two or more genes leads to cell death, whereas a deficiency in only one of these genes does not. the deficiencies can arise through mutations, epigenetic alterations or inhibitors of one or both of the genes. cancer cells are frequently deficient in a dna repair gene. (also see dna repair deficiency in cancer.) this dna repair defect either may be due to mutation or, often, epigenetic silencing (see epigenetic silencing of dna repair). if this dna repair defect is in one of seven dna repair pathways (see dna repair pathways), and a compensating dna repair pathway is inhibited, then the tumor cells may be killed by synthetic lethality. non-tumorous cells, with the initial pathway intact, can survive. ovarian cancer mutations in dna repair genes brca1 or brca2 (active in homologous recombinational repair) are synthetically lethal with inhibition of dna repair gene parp1 (active in the base excision repair and in the microhomology-mediated end joining pathways of dna repair). ovarian cancers have a mutational defect in brca1 in about 18% of patients (13% germline mutations and 5% somatic mutations) (see brca1). olaparib, a parp inhibitor, was approved in 2014 by the us fda for use in brca-associated ovarian cancer that had previously been treated with chemotherapy. the fda, in 2016, also approved the parp inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a brca1 or brca2 gene mutation. colon cancer in colon cancer, epigenetic defects in the wrn gene appear to be synthetically lethal with inactivation of top1. in particular, irinotecan inactivation of top1 was synthetically lethal with deficient expression of the dna repair wrn gene in patients with colon cancer. in a 2006 study, 45 patients had colonic tumors with hypermethylated wrn gene promoters (silenced wrn expression), and 43 patients had tumors with unmethylated wrn gene promoters, so that wrn protein expression was high. irinotecan was more strongly beneficial for patients with hypermethylated wrn promoters (39.4 months survival) than for those with unmethylated wrn promoters (20.7 months survival). the wrn gene promoter is hypermethylated in about 38% of colorectal cancers. there are five different stages of colon cancer, and these five stages all have treatment: stage 0, is where the patient is required to undergo surgery to remove the polyp (american cancer society). stage 1, depending on the location of the cancer in the colon and lymph nodes, the patient undergoes surgery just like stage 0. stage 2 patients undergoes removing nearby lymph nodes, but depending on what the doctor says, the patent might have to undergo chemotherapy after surgery (if the cancer is at higher risk of coming back). stage 3, is where the cancer has spread all throughout the lymph nodes but not yet to other organs or body parts. when getting to this stage, surgery is conducted on the colon and lymph nodes, then the doctor orders chemotherapy (folfox or capeox) to treat the colon cancer in the location needed (american cancer society). the last a patient can get is stage 4. stage 4 patients only undergo surgery if it is for the prevention of the cancer, along with pain relief. if the pain continues with these two options, the doctor might recommended radiation therapy. the main treatment strategy is chemotherapy due to how aggressive the cancer becomes in this stage, not only to the colon but to the lymph nodes. cancer pain management main article: cancer pain symptom control and palliative care although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. in general, doctors have the therapeutic skills to reduce pain including, chemotherapy-induced nausea and vomiting, diarrhea, hemorrhage and other common problems in cancer patients. the multidisciplinary specialty of palliative care has increased specifically in response to the symptom control needs for these groups of patients. pain medication, such as morphine, oxycodone, and antiemetics are drugs to suppress nausea and vomiting. these are very commonly used in patients with cancer-related symptoms. improved antiemetics such as ondansetron and analogues, as well as aprepitant have made aggressive treatments much more feasible in cancer patients. cancer pain can be associated with continuing tissue damage due to the disease process, or the treatment (i.e. surgery, radiation, chemotherapy). there is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, however these are not usually the predominant etiologic factors in patients with cancer pain. some patients with severe pain associated with cancer are nearing the end of their lives, but in all cases, palliative therapies should be used to control the pain. issues such as the social stigma of using opioids and health care consumption can be concerns and may need to be addressed for the person to feel comfortable taking the medications required to control his or her symptoms. the typical strategy for cancer pain management is to get the patient as comfortable as possible using the least amount of medications possible, even if that means using opioids, surgery, and physical measures. historically, doctors were reluctant to prescribe narcotics to terminal cancer patients due to addiction and respiratory function suppression. the palliative care movement, a more recent offshoot of the hospice movement, has engendered more widespread support for preemptive pain treatment for cancer patients. the world health organization also noted uncontrolled cancer pain as a worldwide problem and established a "ladder" as a guideline for how practitioners should treat pain in patients who have cancer cancer-related fatigue is a very common problem for cancer patients, and has only recently become important enough for oncologists to suggest treatment, even though it plays a significant role in many patients' quality of life. mental struggles/pain cancer patients undergo many obstacles and one of these includes mental strain. it is very common for cancer patients to become stressed, overwhelmed, uncertain, and even depressed. the use of chemo is a very harsh treatment causing the cells of the body to die. physical effects like this do not only inflict pain but also cause patients to become mentally exhausted and want to give up. for a lot of reasons including these, hospitals offer many types of therapy and mental healing. some of these include yoga, meditation, communication therapy, and spiritual ideas. all of these are meant to calm and relax the mind, or to give hope for the patients that may feel drained. insomnia a common disorder experienced by people that have survived cancer treatments is insomnia. almost 60% of cancer survivors experience insomnia, and if it is not treated properly it can have long term effects on physiological and physical health. insomnia is defined as dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep. insomnia can heavily reduce one's quality of life. cognitive behavioral therapy has been seen to reduce insomnia and depression for cancer survivors. muscle strength decreased muscle strength is a common side effect to many different cancer treatments. because of this, exercise is very important especially in the first year after treatment. it has been shown that yoga, water exercise, and pilates can improve the emotional well-being and quality of life of breast cancer survivors. hospice in cancer hospice is a group that provides care at the home of a person that has an advanced illness with a likely prognosis of fewer than 6 months. as most cancer treatments involve significant unpleasant side effects, a patient with little realistic hope of a cure or prolonged life may choose to seek comfort care only. this choice of forgoing more radical therapies is an exchange for a prolonged period of normal living. this is an especially important aspect of care for those patients whose disease is not a good candidate for other forms of treatment. in these patients, the risks related to the chemotherapy may be greater than the chance of responding to the treatment, making further attempts to cure the disease impossible. of note, patients in hospice can sometimes still get treatments such as radiation therapy if it is being used to treat symptoms, not as an attempt to cure cancer. during this phase of cancer, it is also important to note that mental health in patients can be greatly affected. advance care planning advance care planning (acp) has been suggest to increase the quality of life of cancer survivors. studies have been done to investigate the effects of acp on lung, heart, and cancer patients and their relatives and its positive effects with decreasing depression and anxiety. acp helps adults at any stage of health decide what they want to do with their future, their goals, and their preferences for medical care. it is very important for the patient to have a voice in how they are treated. research main article: experimental cancer treatment clinical trials, also called research studies, test new treatments in people with cancer. the goal of this research is to find better ways to treat cancer and help cancer patients. clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy. a clinical