Question

2. Review Recent molecular biology advance in tumor diagnosis and treatment ( more than 2000 words)

Answer 1

Cancer is the uncontrolled growth of abnormal cells anywhere in a body due to the accumulation of defects, or mutations, in their DNA. These cells are termed cancer cells, malignant cells, or tumor cells. Most of the time, cells are able to detect and repair DNA damage. If a cell is severely damaged and cannot repair itself, it usually undergoes programmed cell death. Cancer occurs when damaged cells grow, divide, and spread abnormally instead of self-destructing as they should. Causative agents are as follows: chemical or toxic compound exposures, ionizing radiation, some pathogens, and human genetics. There are over 200 types of cancer such as Bladder, Breast, Colorectal Cancer, Endometrial, Kidney (Renal Cell and Renal Pelvis) Cancer, Leukemia (All Types), Lung (Including Bronchus), Melanoma , Non-Hodgkin Lymphoma, Pancreatic, Prostate, Thyroid. Most common cancers gender-wise are Prostate, lung, and colorectal which occurs in men whereas in women, breast, lung, and colorectal cancers are common. Children are mostly diagnosed with leukemia, brain tumors, and lymphoma. Metastasis helps determine the staging and treatment of cancers. Metastasis is the process whereby cancer cells break free from a malignant tumor and travel to and invade other tissues in the body. Cancer cells metastasize to other sites via the lymphatic system and the bloodstream. Cancer cells from the original—or primary—tumor can travel to other sites such as the lungs, bones, liver, brain, and other areas. These metastatic tumors are "secondary cancers" because they arise from the primary tumor. Bladder cancer that metastasizes to the liver is not liver cancer. It is called metastatic bladder cancer.

There are many tests to screen and presumptively diagnose cancer. The diagnosis of cancer typically begins with the detection of symptoms that may be related to the disease. Symptoms associated with cancer vary such as unusual bleeding, persistent cough, changes in bowel or bladder habits, a persistent lump, a sore that does not heal, indigestion or trouble swallowing, and a change in the appearance of a mole or wart. A physical and medical history, especially the history of symptoms, are the first steps in diagnosing cancer. Most of cancers will be determined by the type of cancer and where it is suspected to be located in or on the person's body. Complete blood count, electrolyte levels and, in some cases, other blood studies may give additional information. Imaging studies are commonly used to help physicians detect abnormalities in the body that may be cancer. X-rays, CT and MRI scans, and ultrasound are common tools used. Other tests such as endoscopy, which with variations in the equipment used, can allow visualization of tissues in the intestinal tract, throat, and bronchi that may be cancerous. In areas that cannot be well visualized (inside bones or some lymph nodes, for eg), radionuclide scanning is often used. The test involves ingestion or IV injection of a weakly radioactive substance that can be concentrated and detected in abnormal tissue.

The preceding tests can be very good at localizing abnormalities in the person whereas biopsies, the most-definitive diagnostic tests for cancer, can be performed in the operating room. Biopsies obtained with visual control of an endoscope consist of small fragments of tissue, usually no larger than 5 millimetres (0.2 inch) long. Needle biopsy involves the removal of a core of tissue from a tumour mass with a specially designed needle often under imaging guidance. Alternatively, the needle can be stereotactically guided to a previously localized lesion. This type of biopsy yields a tissue core or cylinder and is frequently used for the diagnosis of breast masses and biopsies of brain lesions. Another type of biopsy, called fine-needle aspiration biopsy, yields cells rather than a tissue sample, so the pathologist is able to assess only cellular features and not the architectural characteristics of the tissue suspected of harbouring a tumour. Nevertheless, fine-needle aspiration has many positive qualities. It is relatively painless and free of complications. In many instances it is a worthwhile adjunct to the diagnosis.

Besides stage and grade, important prognostic factors related to molecular phenomena exist for many types of cancer. DNA sequencing technologies and to the computational approaches have been radically transformed the ability to prognosticate cancer outcome (forecasting the evolution of the tumour and fate of the patient) and the ability to predict how a tumour will respond to a specific drug. Different technologies for tumour profiling, in which many kinds of tumour constituents are detected in a single test, have become used routinely in centres specializing in cancer therapy. Proteomics (the study of protein profiles associated with the genome), patterns of gene activity, and genomics (the study of the genome itself) can be used to identify molecular tumour signatures and thereby enable tumours to be classified on the basis of the molecular defects that cause them. Knowledge of these defects and the abnormal mechanisms by which they produce cancer provides a rational basis for drug design. Neutralizing a cancer-causing molecular mechanism with a drug designed specifically against it can result in direct interference with tumour growth. Demonstration of specific mutations in tumours thus is a crucial part of deciding which drugs to use in a given patient. That is accomplished in part by the sequencing of tumour cell genomes, which provides a sort of bar code of genetic alterations unique to a given tumour. The identification of specific genetic alterations allows physicians to select among an expanding armamentarium of drugs that have been specifically developed to interfere with the abnormal functions associated with tumour mutations.

Molecular alterations also serve as convenient “markers” of disease. In other words, since they are carried in the coded elements contained within tumour cells, their detection in biological fluids or tissues indicates the presence of tumour cells. A sensitive molecular technique known as PCR (polymerase chain reaction) makes it possible to detect mutations that identify certain tumours when only a small number of cancer cells are present. For eg, in leukemia patients who have received bone marrow transplants, PCR may be used to test for residual malignant cells present in very low levels in the circulation. In this way, PCR acts as a sensitive indicator for the success or failure of therapy.

There are many other instances in which PCR and DNA sequencing approaches provide information about cancer treatment and prognosis. For eg, amplification of the gene ERBB2 (also known as HER-2/neu) in breast cancer cells establishes the indication for treatment with a drug called herceptin, which targets the mutated gene product. Neuroblastoma cells that contain amplified amounts of the N-MYC gene indicate a worse prognosis for the individual than do cells from identical tumours that have the normal genetic complement of N-MYC.

Tumour cells also produce substances that appear on their surfaces or are released into the circulation, where they can be detected and measured. Those substances are known as tumour markers. In general, a rising level of a tumour marker in the blood indicates the regrowth of the tumour. Diagnostically useful tumour markers include carcinoembryonic antigen (CEA), which is an indicator of carcinomas of the gastrointestinal tract, lung, and breast; CA 125, which is produced by ovarian cancers; CA 19-9, which is an indicator of pancreatic or gastrointestinal cancers; and alpha-fetoprotein and chorionic gonadotropin, which can indicate testicular cancer.

The diagnostic tests that are necessary to identify genetic alterations and tumour markers and thereby predict the efficacy of a drug are sometimes referred to as companion diagnostics. Three main genetic cancer causing mechanisms have been identified: chromosomal translocation, gene amplification, and point mutation.

Treatment

The cancer treatment is based on the type of cancer and the stage of the cancer. In some people, diagnosis and treatment may occur at the same time if the cancer is entirely surgically removed when the surgeon removes the tissue for biopsy. Most treatments have one or more of the following components: surgery, chemotherapy, radiation therapy, or combination treatments (a combination of two or all three treatments). Individuals obtain variations of these treatments for cancer. Patients with cancers that cannot be cured (completely removed) by surgery usually will get combination therapy, the composition determined by the cancer type and stage. Other treatments include targeted/biological therapies, hematopoietic stem cell transplants, angiogenesis inhibitors, cryosurgery, and photodynamic therapy. Every treatment has potential risks, benefits, and side effects. The patient and his or her care team, which may include an internist or other specialist, surgeon, oncologist, radiation oncologist, and others, will help determine the best and most appropriate course of treatment.

Surgery is often performed to remove malignant tumors. Surgery allows for the determination of the exact size of the tumor as well as the extent of spread and invasion into other nearby structures or lymph nodes – all-important factors in prognosis and treatment. Surgery is often combined with other cancer treatments, such as chemotherapy and/or radiation. Sometimes, cancer cannot be entirely surgically removed because doing so would damage critical organs or tissues. In this case, debulking surgery is performed to remove as much of the tumor as is safely possible. Similarly, palliative surgery is performed in the cases of advanced cancer to reduce the effects of a cancerous tumor. Radiation is a very common cancer treatment. About 50% of all cancer patients will receive radiation treatment, which may be delivered before, during, or after surgery and/or chemotherapy. Radiation can be delivered externally -- where X-rays, gamma rays, or other high-energy particles are delivered to the affected area from outside the body -- or it can be delivered internally. Internal radiation therapy involves the placement of radioactive material inside the body near cancer cells. This is called brachytherapy. Systemic radiation involves the administration of radioactive medication by mouth or intravenously. The radioactive material travels directly to the cancerous tissue. Radioactive iodine (I-131 for thyroid cancer) and strontium-89 (for bone cancer) are systemic radiation treatments. Typically, external radiation is delivered 5 days a week over the course of 5 to 8 weeks. Other treatment regimens are sometimes used. One of the most life-threatening effects of high doses of chemotherapy—and of radiation as well—is damage that can be done to bone marrow. Marrow is found within the cavities of bones. It is rich in blood-forming (hematopoietic) stem cells, which develop into oxygen-bearing red blood cells, infection-fighting white blood cells, and clot-forming platelets. Chemotherapy can decrease the number of white blood cells and reduce the platelet count, which in turn increases susceptibility to infection and can cause bleeding. Loss of red blood cells also can occur, resulting in anemia.

In addition to surgery, radiation, and chemotherapy, other therapies are used to treat cancer. Targeted or biological therapies seek to treat cancer and boost the body's immune system while minimizing damage to normal, healthy cells. Monoclonal antibodies, immunomodulating drugs, vaccines, and cytokines are targeted or biological therapies. Hematopoietic stem cell transplants involve the infusion of stem cells into a cancer patient after the bone marrow has been destroyed by high-dose chemo and/or radiation. Angiogenesis inhibitors are medications that inhibit the growth of new blood vessels that cancerous tumors need in order to grow. Cryosurgery involves the application of extreme cold to kill precancerous and cancerous cells. Photodynamic therapy (PDT) involves the application of laser energy of a specific wavelength to tissue that has been treated with a photosensitizing agent, a medication that makes cancerous tissue susceptible to destruction with laser treatment. Photodynamic therapy selectively destroys cancer cells while minimizing the damage to normal, healthy tissues nearby. Knowledge about the genetic defects that lead to cancer suggests that cancer can be treated by fixing those altered genes. One strategy is to replace a defective gene with its normal counterpart, using methods of recombinant DNA technology. Methods to insert genes into tumour cells and to introduce genes that alter the tumour microenvironment or modify oncolytic viruses to make them more effective are of particular interest. Other biological response modifiers that have been developed include interferon, tumour necrosis factor, and various interleukins. Interleukin-2 (IL-2), stimulates the growth of a wide range of antigen-fighting cells, including several kinds that can kill cancer cells. One use of IL-2 is to expand immune cells collected from a patient’s blood. The patient’s immune cells are genetically engineered in the laboratory to stimulate the expansion of T cell populations against IL-2-expressing tumour cells. The engineered cells are then infused into the patient in great numbers to fight the cancer.