Carboplatin

Structures of the platinum analogues. cis configuration of platinum in its +2 oxidation state, designated as Pt(II). The cis isomers are cytotoxic whereas the trans isomers are much less potent. In addition to the oxidation state and isomeric configuration, clinical activity and toxic-ity of the platinum analogues seem to be related to the type of carrier ligand and leaving groups attached to the core cis-platinum structure. As shown in Figure 2.4, carboplatin differs from cisplatin...

Topoisomerase ITargeting Agents

Camptothecin (CPT), a naturally occurring, relatively water-insoluble alkaloid extract from the bark and wood of the Chinese tree Camptothecan acuminata, is the prototype topoisomerase I-targeting agent. Its clinical development was halted early due to its toxicity and only upon the introduction of water-soluble forms was it reintroduced into clinical testing. The analogues have greater in vivo and in vitro activity and less severe and more predictable toxicity than camp-tothecin. All CPT...

Weighing Benefits and Harms Decision Making About Screening

Weighing the benefits and harms of screening programs is difficult. First, one must determine the presence and magnitude of the benefits and harms. Benefits seem intuitive, but closer inspection shows that they are easy to overestimate. Evidence about the accuracy or yield of screening tests by itself is inadequate, as is evidence about the effectiveness of treatment in people detected clinically. Etiologic data about trends in mortality over time are open to multiple interpretations. To avoid...

Mechanisms of Immunosuppression in Cancer Patients

Cancers have multiple mechanisms that prevent the activation of, and evade, the immune response, as described next (Table 20.6). It is likely that a therapeutic vaccine may not be an adequate immunotherapy without the means to overcome immunosuppression. With adequate knowledge of how tumors evade T-cell-mediated rejection, strategies are being developed that should improve the efficacy of cancer immunotherapy. TABLE 20.6. Mechanisms of immunosuppression in cancer Tumor-derived immune...

Hormone Receptor Targeted Therapies

Targeting hormonal growth pathways has been an effective strategy in the management of various tumors such as breast, prostate, and endometrial cancers. Early approaches were directed at surgical ablation of the glands supplying these hormonal stimuli (i.e., ovariectomy for breast cancer and orchiectomy for prostate cancer), but over the pst 30 years a large number of medical agents have become available based on an increasing understanding of molecular endocrinology. Medical endocrine...

Medullary Thyroid Cancer

Increased genetic knowledge has also changed our approach to thyroid cancer. Medullary thyroid cancer (MTC) is a well-established component of multiple endocrine neoplasia syndrome type 2a (MEN 2a) or type 2b (MEN 2b). Previously, family members at risk for MEN 2 underwent annual screening for elevated calcitonin levels however, this only detected MTC after it developed. In 1993 it was identified that mutations in the RET proto-oncogene were present in almost all cases of MEN 2a and 2b. Now...

Breast Cancer

Another example of prophylactic surgery is the bilateral mastectomy for women at high risk of developing breast cancer. Before the identification of the BRCA genes, prophylactic mastectomies were typically reserved as an option for women with lobular carcinoma in situ (LCIS). However, with the identification of BRCA1 and BRCA2, the role of prophylactic mastectomies has been greatly expanded. For women with BRCA1 or BRCA2 mutations, the lifetime probability of breast cancer is between 40 and 85...

Botanical Herbal Medicines Used Against Cancer

Medicines derived from whole plant extracts, and which therefore contain many different types of molecules, are generally described as herbal medicines. The term botanical is used here to reflect that such agents are obtained from a wide variety of natural products, not just from herbs. Medicinal botanicals are minimally toxic, particularly when compared with plant-derived chemotherapeutic agents, and they are readily available without prescription. Described next are some botanicals commonly...

Goldie and Coldman Hypothesis

An important corollary to tumor growth is the development of drug resistance resulting from spontaneous mutations that occur with cell proliferation, independent of the resistance inherent to the heterogeneity in cell kinetics described earlier. Goldie and Coldman had hypothesized that this occurs at a rate of 1 of 105 cells per gene.7 If 1g tumor, the minimum size for detection, contains 109 cells, then such a tumor might contain 104 clones resistant to any given drug. However, resistance to...

Growth Factor Receptor Targeted Therapies

In human cancer cells, aberrant signaling through the epidermal growth factor receptor (EGFR) has been associated with neoplastic cell proliferation, resistance to apoptosis, migration and stromal invasion, and enhanced angiogenesis. The EGFR (or ErbB-1) is part of a subfamily of four closely related receptors that include HER-2 neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4).5 These receptors exist as inactive transmembrane monomers in cells, and dimerize after ligand activation either by...

Skippers Exponential Tumor Growth LogKill Hypothesis

One of the pioneer investigations in tumor growth kinetics was made by Skipper and his colleagues,3 who described the first model of tumor growth kinetics. Despite its flaws and oversimplified nature, the empiric observations derived from this model underlie many of the tenets in cancer chemotherapy. A conclusion derived from his L1210 mouse leukemia model was the exponential (logarithmic) growth of tumor cells. Doubling time of cancer cells was proposed to be constant, yielding a straight line...

A

A 26-year-old woman with previous history of talc pleurodesis for malignant pleural effusion. (A) FDG-PET scan shows areas of increased uptake in the pleural space (arrows). (B) Correlative CT scan (soft tissue windows) shows increased attenuation (arrows) in the pleural space consistent with talc deposits. The patient had no clinical evidence for recurrence, and her PET and CT scans were stable over 3 years. 1. Fry WA, Menck HR, Winchester DP. The National Cancer Data Base report...

Multiple Endocrine Neoplasias MEN Types 1 and

The familial MEN syndromes are characterized by clustering of benign and malignant endocrine tumors and other systemic manifestations. MEN type 1 includes combinations of more than 20 different types of tumors, but the most characteristic are tumors of the parathyroid, pituitary, and pancreatic glands. The term multiple refers both to the occurrence of multiple tumors in the same gland and to multiple different kinds of tumors in the same individual and or family. MEN1 is inherited as an...

Ovarian Cancer

Because of paucity of symptoms in early stages, approximately 60 to 75 of patients with ovarian cancer present with advanced disease.93,114 Ovarian cancer is staged surgically according to the FIGO staging system. The FIGO system reflects the three primary mechanisms of disease spreads of ovarian cancer, including local, peritoneal, and lymphatic. In most centers, endovaginal ultrasound is the primary imaging modality used for screening for ovarian cancer and evaluation of an adnexal mass....

Voriconazole 103451

Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma see comments . N Engl J Med 1995 333 1540-1545. 2. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome see comments . N Engl J Med 1996 335 91-97. 3. Child JA, Morgan GJ, Davies FE, et...

Genetic Counseling

The development of technology to locate and isolate cancer susceptibility genes has brought together the fields of oncology, cancer control, genetics, and genetic counseling to create a new specialty of cancer risk counseling whose goal is to communicate more accurate information about personal cancer risk profiles based on personal and family histories.13 The field of genetic counseling has evolved and plays a growing role in the evaluation and risk estimation of families with known or...

Nathan Levitan Meri Armour and Afshin Dowlati

In recent decades, cancer treatment has evolved from a purely surgical approach to the complex coordination of sophisticated surgery, radiotherapy, and chemotherapy. The technology associated with pain and nutrition management has improved,1-3 and the importance of psychosocial factors in the treatment of cancer patients has been recog-nized.4 The knowledge base pertaining to cancer treatment has become so vast that many physicians have developed sub-specialty expertise in a focused aspect of...

Antitumor Antibiotics and Related Synethetic Compounds

Most of the antitumor antibiotics were initially isolated from various Streptomyces species. Central to their cytotoxic profile is the presence of numerous mechanisms by which each individual antibiotic interacts with DNA. The variety of chemical structures present in each compound participate in multiple mechanisms responsible for their activity against cells. The polycyclic chromophore structure intercalates with DNA and is also responsible for conferring the characteristic bright color of...

Chemotherapy Approaches in the Management of Cancers

Cancer chemotherapy has principally been used in the management of advanced or metastatic disease, following failed local therapies, or in disease for which no alternative therapy is effective. Chemotherapy is curative for several advanced human cancers, such as gestational trophoblastic disease, certain hematologic malignancies, or germ cell testicular cancer. However, most common solid tumors are not curable with current chemotherapeutic regimens when metastatic (Table 2.1). The roles of...

B

Punch biopsy of large cutaneous lesions. (A) Schematic view demonstrating that all layers of the skin can be sampled using this technique. (B) Different size punch biopsy tools that can be used. (A From Arca MJ, Biermann JS, Johnson TM, et al.,32 by permission of Surgical Oncology Clinics of North America.) figure 4.6. Schematic diagram illustrating the lymphatic drainage of the breast and sentinel lymph nodes. TABLE 4.3. Potential indications for prophylactic organ removal....

FDGPET in the Diagnosis and Staging of Recurrent Colorectal Cancer

Early detection of recurrent disease is of primary importance because it may lead to a cure in up to 25 of patients. Surgical or medical treatment with the intent to improve survival and the quality of life should be guided by the accurate staging of disease. The size and number of hepatic metastases and the presence of extrahepatic disease affect the prognosis. The prognosis is poor if extrahepatic metastases are present, and this is believed to be a contraindication to hepatic resection.255...

Hypercoagulability

Cancer is associated with hypercoagulability and an increased risk of venous thrombosis or pulmonary embolism. This susceptibility can be compounded by decreased mobility resulting from fatigue and diminished functional status, or by pain related to the operative procedure. Operations particularly of risk include operations of the abdomen, pelvis, hip, or leg. Surgery that is of long duration, which uses laparoscopy, or has a degree of postoperative immobilization adds additional risk. Cancer...

M

Cell-cycle-specific chemotherapeutic drugs and specific cell-cycle phase. figure 2.3. Cell-cycle-specific chemotherapeutic drugs and specific cell-cycle phase. proliferating, that is, in cycles other than resting GO phase (Figure 2.3). Moreover, these drugs are usually most active in a specific phase of the cell cycle. Cell-cycle-specific drugs include the antimetabolites, antitubulin agents, and drugs targeting topoisomerase. Tables 2.3 and 2.4 describe common toxicities for each...

Targeting DNA Repair for Tumor Radiosensitization

As reviewed previously in this chapter, recent advances in our understanding of DNA repair have shown genetic and epigenetic changes in several common human cancers, which result in alterations in IR damage recognition and damage repair processes. DNA mismatch repair (MMR) is a postrepli-cational process whose genes proteins are not only capable of recognizing and processing single DNA base-pair mismatches and insertion-deletion loops during DNA replication, but also DNA adducts resulting from...

FDGPET for Predicting Treatment Response

Evaluation of PET for assessment of treatment response has been studied more extensively in HD and NHL than in any other tumor. Differentiation of viable tumor from fibro-sis in a residual posttreatment mass is a common problem in lymphoma that is seen in more than 85 of patients with HD and approximately 40 of the patients with NHL. Initial studies have assessed response to treatment in heterogeneous populations including both HD and NHL patients. Cremerius et al.324 reported better...

Principles of Chemotherapy

During World War II, sailors who were accidentally exposed to nitrogen mustard following the explosion of a ship developed marrow and lymphoid hypoplasia.1 This serendipitous discovery led to the first clinical trial conducted in 1942 using nitrogen mustard in patients with malignant lymphomas at Yale University.2 This marked the beginning of a new era of research in the quest for effective and safe drugs used in cancer chemotherapy. The term chemotherapy has been loosely applied to the myriad...

Contributors

Professor, Department of Oncology, Mayo Clinic Foundation, Rochester, MN, USA. Staff Scientist, Department of Clinical Bioethics, Warren G. Magnuson Clinical Center and Medical Oncology Research Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Chair Emeritus, F.A. David Professor, and Lorenz E. Zimmerman Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA. Associate Professor, Department of Medicine,...

References

Breast Cancer and Its Diagnosis and Treatment. Baltimore Williams & Wilkins, 1955. 2. Rutledge RH. Theodore Billroth a century later. Surgery (St. Louis) 1995 118 36-43. 3. Weir R. Resection of the large intestine for carcinoma. Ann Surg 1886 1886(3) 469-489. 4. Halsted WS. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June 1889 to January 1894. Ann Surg 1894 320(13) 497-555. 5. Clark JG. A more radical method for...

Recommendations of Professional Groups Overweight and Obesity

In the year 2000, the National Heart, Lung and Blood Institute, in partnership with the North American Association for the Study of Obesity, released The Practical Guide Identification, Evaluation and Treatment of Overweight and Obesity in Adults.100 These guidelines defined a healthy body weight, based on the body mass index (BMI) weight in kilograms (height in meters)2 between 18.5 and 25.0.100 According to these guidelines, individuals are considered to be overweight if the BMI is between 25...

Multistage Carcinogenesis Process and Targets for Prevention

Humans are exposed to a wide variety of endogenous and exogenous carcinogenic insults, including chemicals, radiation, physical agents, bacteria, and viruses. Recent progress in the study of the multistep process of carcinogenesis, particularly on the mechanisms of chemically and virally induced cancer, has revealed several points along the car-cinogenesis pathway that may be amenable to cancer prevention strategies. The classic view of experimental car-cinogenesis, in which tumor initiation is...

False Positive Test Results

False-positive screening test results can cause harm both psychologically and by adverse effects from unnecessary workups. Although a positive screening test does not mean that one has the disease in question, it does mean a person has been placed into a higher risk group than previously. That is, the risk of having breast cancer is higher among women with a positive mammogram than among women who have not yet had a mammogram. The individual may experience the uncertainty of not knowing whether...

Ionizing Radiation Effects on the Cell Cycle

It has been known for several decades that ionizing radiation leads to a prolongation of the cell cycle and can result in an arrest in the G1, G2, and S phases.7,19,20 Because ionizing radiation causes a variety of DNA damage, it was initially inferred that these cell-cycle arrests (now called checkpoints) were essential for the repair of these different types of DNA damage. However, over the past 10 to 15 years, the biology of the cell cycle has become better understood as a complex but finely...

Info

First use of comparison groups in a clinical experiment First application of mathematical analysis to test a hypothesis Introduction of concept of confounding (i.e., patients' response may vary for reasons other than treatment) First systematic use of statistics in medicine Development of systematic data collection Calculation of rates of morbidity and mortality, based on hospital intake and discharge data Development of statistical methods accounting for the role of chance in scientific...

Retroviruses

Human T-Cell Leukemia Virus Types I and II Human T-cell leukemia viruses type I (HTLV-I) and type II (HTLV-II) belong to the subfamily Oncovirinae of the family Retroviridae. HTLV-I infection is endemic in Japan, other regions of Asia such as the Philippines, the Caribbean region, central Africa, and some areas of Australia and New Guinea. In these areas of the world, the seroprevalence rate of antibodies to HTLV-I is 5 to 33 in the normal human popu-lation.207 HTLV-I is associated with adult...

Case Study IV Tamoxifen and Breast Cancer

Breast cancer is the most common noncutaneous cancer among women in the United States.57 Although breast cancer mortality has declined in the United States over the past decade, it remains the second leading cause of cancer-related deaths in women, after lung cancer.58 Approximately 211,300 women in the United States were diagnosed with invasive breast cancer in 2004, and about 39,800 women will have died Hormonal therapy has an important place in the treatment and prevention of breast cancer....

Randomization and Clinical Equipoise

Randomized controlled trials (RCTs) permit the comparison of standard care with one or more new interventions. RCTs are the gold standard of clinical research. Controls and some form of randomization have been used for about 100 years,11 although the first modern randomized, placebo-controlled trial was conducted only in 1948 to evaluate streptomycin for pulmonary tuberculosis.12 There are many concerns about the ethics of randomization, including the need for researchers to suspend their...

Repair of Ionizing Radiation Damage Cellular and Molecular Mechanisms

As mentioned, ionizing radiation can cause a variety of lesions through direct interactions with DNA or, more commonly, through damage induced in adjacent water molecules within a cell or adjacent cells. These damages to DNA include damage to the deoxyribose backbone, base damage, single-strand breaks (SSBs), and double-strand breaks (DSBs).4 Because exposure to ionizing radiation was inevitable during evolution, human cells have developed multiple repair pathways to handle the diverse types of...

Contents

Hortobagyi vii xiii 1 Evidence-Based Approach to Oncology 3 2 Principles of Chemotherapy 14 3 Principles of Radiation Oncology 41 Timothy J. Kinsella, Jason Sohn, and Barry Wessels 4 Principles of Surgical Therapy in Oncology 58 Michael S. Sabel, Kathleen M. Diehl, and Alfred E. Chang 5 Principles of Targeted and Biological Therapies 73 Stephen R.D. Johnston, Sue Chua, and Charles Swanton 6 Biologic Principles of Hematopoietic Stem Cell Transplantation 91 7 Evaluation of...

Vinca Alkaloids

Most antimicrotubules agents are alkaloids, structurally complex plant-derived organic bases. Vinca alkaloids are the first widely used class of antimicrotubule agents in cancer chemotherapy. They are cell-cycle-specific vesicants derived from the pink periwinkle plant, Catharanthus roseus (L.) G. Don. Vincristine and vinblastine are the two representative compounds. Vinorelbine is a vinblastine semisynthetic derivative with broad antitumor activity as a single agent that may not be completely...

Receptor Tyrosine Kinase Inhibition

By far the most successful approach to targeting the RAS pathway in cancer has been to develop inhibitors of upstream activators of RAS. The development of inhibitors for specific RTKs limits the utility of these drugs to cancers where that particular RTK is overactive, but given these constraints, this class of drugs seems highly effective. RTKs play prominent roles in many cancers, ranging from non-small cell lung cancer to breast cancer to gastrointestinal stromal tumors, which often feature...

Prostate Cancer

Accurate staging of prostate cancer is essential for the prognosis and treatment planning. In particular, it is crucial to determine the local extent of prostate cancer (extracapsular extension and seminal vesicle infiltration) and the presence of metastatic disease (lymphatic or hematogenous), because radical prostatectomy is the preferred method of treatment for patients with disease confined to the capsule. Patients with disease outside the prostate are generally not surgical candidates and...

Case Study V Finasteride and Prostate Cancer

The Prostate Cancer Prevention Trial (PCPT) is a doubleblind chemoprevention trial of prostate cancer in 18,882 non-symptomatic, healthy men who were randomized to 5 mg day of finasteride or placebo for 7 years.79 Finasteride is an inhibitor of ( 90 of) 5-a-reductase, an enzyme involved in hormone metabolism of testosterone to dihydrotestosterone (DHT), the most active androgen in the prostate. Intraprosta-tic DHT is thought to be a major stimulus for prostate cancer cell growth, as evidenced...

Bronchogenic Carcinoma

Lobe Resection Lung

A patient with bronchogenic carcinoma may report symptoms including cough, sputum production, or hemoptysis at first presentation for evaluation by a physician. Other patients have advanced disease and nonspecific systemic symptoms, including weight loss and weakness, at initial examination. Chest radiographs may show findings that suggest lung cancer. Still other patients report no symptoms related to lung cancer, and abnormal results on chest radiographs prompt further workup. In almost 40 of...

Adrenal Gland

Adrenal Adenoma and Differentiation from Other Adrenal Masses Incidental discovery of adrenal masses is a common clinical problem as a result of the widespread use of imaging procedures, occurring in up to 5 of patients who have undergone abdominal CT.57 Most adrenal masses are benign nonhyper-functioning adenomas even in patients with a known extra-adrenal malignancy (Figure 31.9).57 Primary adrenal carcinoma is rare, with a reported incidence of 2 cases per million (Figure 31.10)....

Asbestos General Aspects of Exposure

Asbestos, a group of naturally occurring, fibrous silicate minerals, include the serpentine mineral, chrysotile, and five amphibole minerals (actinolite, amosite, anthophyllite, cro-cidolite, and tremolite)64 (Table 18.2). Chrysotile, anthophyl-lite, amosite, and crocidolite are the only forms that have been used commercially.65 However, tremolite can be a contaminant in chrysotile and talc deposits, and actinolite is a common contaminant in amosite deposits.2 Occupational exposure to...

Summary and Conclusion

This chapter has reviewed the evidence related to the epidemiology, natural history, and screening of four common cancers (breast, cervical, colorectal, and prostate). It presents this evidence within the context of the challenges of primary care practice and emphasizes the need to view cancer screening as a process of care. Ensuring access to screening and treatment for all is necessary to achieve the potential for mortality reduction afforded by current screening technologies. Regardless of...

Russell Harris and Linda S Kinsinger

Creening is defined as testing for a condition when the person has no recognized signs or symptoms of that condition. The purpose of screening is not to merely detect a condition, but rather to help people live better or longer. This is an important distinction the detection of earlier disease by itself is insufficient to justify a screening program. The program must additionally demonstrate that people live longer or better because of the earlier detection. A positive screening test result...

Foreword

Compared to more traditional subspecialties, oncology is a young, vibrant, and progressive branch of medicine that has relatively few ties to a dogmatic past. Perhaps for this reason many innovations in oncology have occurred as a consequence of rapid cultural changes within the specialty, and continued change remains an accepted and integral part of our field. While most other practitioners of medicine learned a standard of practice and some dedicate their practice to clinical and or basic...

Polyaromatic Hydrocarbons

Poly aromatic hydrocarbons are a group of more than 100 ubiquitous environmental contaminants that occur naturally in coal, crude oil, and gasoline and are produced mainly from incomplete combustion of fossil fuels. PAHs are found in tobacco smoke, smoke from wood-burning stoves and fireplaces, and motor vehicle exhaust.2 Additionally, smoking or charbroiling meat can increase the formation of PAHs.29 Aside from occupational exposure, humans can potentially come into contact with PAHs through...

Papovaviruses

BK Virus, JC Virus, and Simian Virus 40 BK virus (BKV), JC virus (JCV), and simian virus 40 (SV-40) belong to the family of Papovaviridae. The three viruses are similar in structural and functional properties.64,65 Nucleotide sequence homology of the three viruses is 68 to 72 , and protein sequence homology is 76 to 90 in different regions of the viral genomes.64 Primary infection by BKV and JCV occurs in childhood and is usually unapparent. During primary infection, the virus spreads by...

Hereditary Colorectal Cancer Syndromes Fap Hnpcc

The adenomatous polyposis coli (APC) gene on chromosome 5q21 encodes a protein that is important in cell adhesion, signal transduction, and transcriptional activation. Germ-line mutations in APC are associated with familial adenomatous polyposis (FAP), a syndrome whose clinical phenotype includes hundreds to thousands of adenomatous polyps in the colon and rectum developing after the first decade of life and a 90 risk of developing colorectal cancer by the fourth decade of life.88 Additional...

Some Additional Topics

Confirmatory Trials and Meta-Analyses Because of the planning, infrastructure, cost, and time required, Phase III trials are carefully designed to avoid equivocal findings, and thus provide definitive evidence for or against changes in therapy standards. Nonetheless, questions regarding the treatments under evaluation will invariably remain unanswered, and thus there is an important role for replicated (referred to as confirmatory) trials and the synthesis of similar trials into a coherent body...

Efficacy of Risk Reduction Alcohol Abuse

Nearly one-third of U.S. adults drink an excessive amount of alcohol.26 Excessive alcohol use appears to be associated with cancers of the breast, oropharynx, pharynx, esophagus, and liver.27-31 Little evidence exists examining the effect on changes in alcohol consumption on the risk of breast or other cancers. Two studies from Italy observed that, although stopping smoking decreased the risk of laryngeal cancer within only a few years, stopping drinking led to a much smaller decline in...

Example of Cervical Cancer Screening

In 2004, an estimated 10,520 new cases of and 3,900 deaths from invasive cervical cancer were expected.20 In 2000, the age-adjusted incidence rate in nine Surveillance, Epidemiology, and End Results Program (SEER) registries was 8 per 100,000 women the age-adjusted mortality rate was 3 per 100,000.21 From 1950 to 1970, the incidence and mortality rates of invasive cervical cancer fell impressively by more than 70 . From 1970 to 2000, the rates continued to decrease by more than 40 .22 This...

Folate Antagonists

5fu Mucositis Mechanism

Folates exist predominantly as polyglutamates within cells to facilitate intracellular retention in excess of the freely trans portable monoglutamate form. They must first be reduced to tetrahydrofolate FH4 by the enzyme dihydrofolate reductase DHFR to become active coenzymes in one-carbon transfer reactions, among which are those required for the de novo purine synthesis mediated by glycineamide ribonucleotide formyltransferase GARFT and aminoimidazole carboxamide ribonucleotide transformylase...