ONCOLOGY
Overview:
In 2016, approximately 1.68 million new cancer cases were diagnosed in the USA, and nearly 600,000 individuals are expected to die from this disease. Cancer is the second most common cause of death in the United States, accounting for 1 in 4 deaths. It is characterized by a defect in the normal control mechanisms that govern cell survival, proliferation and differentiation.
Cells that undergo neoplastic transformation, express cell surface antigens that may be of the normal fetal type, and may display other signs of apparent immaturity. They may exhibit qualitative or quantitative chromosomal abnormalities, including various translocation and appearance of amplified gene sequences.
The invasive and metastatic processes of genetic instability, as well as a series of metabolic abnormalities associated with cancer, result in tumour-related symptoms and eventual death of a patient unless the neoplasm can be eradicated with treatment.
Therapeutic indications of various cancers:
Chronic myelogenous leukaemia:
It arises from a chromosomally abnormal hematopoietic stem cell in which a balanced translocation between the long arms of chromosomes 9 and 22 is observed in 90–95% of cases. Symptoms are related to WBCs count and its rate of increase. The tyrosine kinase inhibitor is used as first-line therapy.
Multiple myeloma:
This is a plasma cell malignancy arising from a single tumour stem cell. The tumour cells moreover assemble a marker protein (myeloma immunoglobulin) that permits the total body burden of tumour cells to be quantified. Multiple myeloma principally involves the bone marrow and bone, causing bone pain, lytic lesions, bone fractures, and anaemia as well as increased susceptibility to infection.
Prostate cancer:
It is the cancer of the prostate gland in males that may spread to other body parts such as bones and lymph nodes. Initially, there are no symptoms but later symptoms include pain and difficulty in urination, blood in urine or pain in the pelvis or back. Late symptoms include fatigue due to low levels of RBCs.
Colorectal cancer:
It is the most common type of gastrointestinal malignancy. Nearly 150,000 new cases are diagnosed each year in the USA.it originates in secretory cells lining the gut. Risk factors include low vegetable fibre and high fat in the diet. It can be diagnosed through the bleeding of a polyp, colicky bowel pain, and bowel obstruction.
Lung cancer:
It is a malignant lung tumour characterized by abnormal cell growth in the tissues of the lung and can spread to other associated parts by the process of metastasis. Symptoms are coughing with blood, weight loss, shortness of breath and chest pains. Most lung cancers are due to long-term tobacco smoking. It can be diagnosed on chest radiographs and computed tomography.
Ovarian cancer:
In the majority of the patients, ovarian cancer remains occult and becomes asymptomatic only after it has already metastasized to the peritoneal cavity. At this stage, it usually presents with malignant ascites. It can be diagnosed with laparoscopy, ultrasound, and CT scanning. Its risk factors include hormone therapy after menopause, fertility medications, and obesity.
Testicular cancer:
It develops in the testicles of the male reproductive system characterised by a lump in the testicle, or swelling or pain in the scrotum. If it is treated, it may result in infertility. Treatment of testicular cancers includes surgery, radiation therapy, chemotherapy, or stem cell transplantation.
Other malignant cancers are breast cancer, childhood leukaemia, adult leukaemia, brain cancer, malignant melanoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, and gastrointestinal cancers include oesophagal cancer, stomach cancer, pancreatic cancer, hepatocellular carcinoma, gallbladder cancer, cholangiocarcinoma, MALT lymphoma and other gastrointestinal stromal tumours.
Chemotherapy stages:
Chemotherapy has been used in three main clinical settings for years. These are;
1. Primary induction treatment for cancers for which there are no other effective treatment approaches.
2. Neoadjuvant treatment for the patients with localized disease and for whom local forms of therapy are surgery or radiation, or both.
3. Adjuvant treatment to local methods of treatments, including surgery and radiation therapy.
Drug indications with classes.
Alkylating agents:
Drugs mechlorethamine (for Hodgkin’s and non-Hodgkin’s lymphoma), chlorambucil, cyclophosphamide (for breast, ovarian cancer and other tumours), bendamustine, melphalan, thiotepa, busulfan, carmustine, lomustine and altretamine (for ovarian cancer) form DNA cross-links, resulting in inhibition of DNA synthesis and function. Their acute toxicity includes nausea and vomiting.
Other drugs cisplatin, carboplatin and oxaliplatin form intrastrand and interstrand DNA cross-links; binding to nuclear and cytoplasmic proteins.
Natural product cancer chemotherapy drugs:
Bleomycin acts as oxygen-free radicals that bind to DNA causing single and double-strand DNA breaks. It is used to treat Hodgkin’s and non-Hodgkin’s lymphoma, germ cell cancer, and head and neck cancer.
Mitomycin acts as an alkylating agent and forms cross-links with DNA and forms oxygen-free radicals that target DNA. It is used to treat superficial bladder cancer, gastric cancer, breast cancer, non-small cell lung cancer, and neck and head cancer.
Vinblastine and vincristine, both inhibit mitosis and are used to treat Hodgkin’s and non-Hodgkin’s lymphoma.
Other drugs of this class are daunorubicin, docetaxel, doxorubicin, etoposide, idarubicin, irinotecan, paclitaxel, topotecan and vinorelbine.
Miscellaneous anticancer drugs:
Bortezomib and carfilzomib act as inhibitors of 26S proteasome, resulting in down-regulation of the NF-KB signalling pathway. These drugs are used in multiple myeloma. Bortezomib is also used in mantle cell lymphoma.
Cetuximab drug binds to EGFR and inhibits downstream EGFR signalling; enhances response to chemotherapy and radiotherapy. It is used in colorectal cancer, head and neck cancer and non-small cell lung cancer.
Other drugs in this group are erlotinib, imatinib, bosutinib, panitumumab, bevacizumab, sorafenib, sunitinib and pazopanib.
Antimetabolites:
Capecitabine and 5-fluorouracil drugs inhibit TS, incorporation of FUTP into RNA resulting in an alteration in RNA processing. They also cause the incorporation of FdUTP into DNA resulting in inhibition of DNA synthesis and function. They are used to treat colorectal cancer, gastroesophageal cancer and hepatocellular cancer. Capecitabine is also used in breast cancer treatment.
Pemetrexed drug inhibits TS, DHFR, and purine nucleotide synthesis used to treat mesothelioma and non-small cell lung cancer.
Other drugs in this class include methotrexate, cytarabine, gemcitabine, fludarabine, cladribine, 6-mercaptopurine and 6-thioguanine.
