Fighting Cancer with Knowledge and Hope provides you with the infor-
mation you need to survive cancer. But above everything else, Dr. Frank
gives you the wisdom to knock out the despair and depression brought
on by cancer. He gives you a needed dose of tranquillity.
Lung cancer is the leading cause of cancer death among men and women in
the United States with 170,000 deaths per year. This exceeds the sum of the
next three leading causes of death due to cancer: breast, colon, and prostate.
There are over 1 million deaths worldwide due to lung cancer, making it truly
an epidemic. Fewer than 15% achieve a 5-yr survival. The vast majority (85%)
present with advanced disease, although stage I patients may have a 5-yr
survival approaching 70% (1).
Harrison's Internal Medicine Chapter 80. Cancer Cell Biology and Angiogenesis
Cancer Cell Biology and Angiogenesis: Introduction Two characteristic features define a cancer: unregulated cell growth and tissue invasion/metastasis. Unregulated cell growth without invasion is a feature of benign neoplasms, or new growths. Cancer is a synonym for malignant neoplasm. Cancers of epithelial tissues are called carcinomas; cancers of nonepithelial (mesenchymal) tissues are called sarcomas. Cancers arising from hematopoietic or lymphoid cells are called leukemias or lymphomas.
Other Nonmelanoma Cutaneous Malignancies
Neoplasms of cutaneous adnexa and sarcomas of fibrous, mesenchymal, fatty, and vascular tissues make up 1–2% of NMSC (Table 83-6). Some can portend a poor prognosis such as Merkel cell carcinoma, which is a neural crestderived, highly aggressive malignancy that exhibits a metastatic rate of 75% and a 5-year survival rate of 30–40%. Others, such as the human herpes virus 8-induced, HIV-related Kaposi's sarcoma, exhibit a more indolent course.
VEGF and its receptors are required for vasculogenesis (the de novo formation of blood vessels from differentiating endothelial cells, as occurs during embryonic development) and angiogenesis under normal (wound healing, corpus luteum formation) and pathologic processes (tumor angiogenesis, inflammatory conditions such as rheumatoid arthritis).
Treatment of Metastatic Disease
Melanoma can metastasize to any internal organ, the brain being a particularly common site. Metastatic melanoma is generally incurable, with survival in patients with visceral metastases generally
PI3K is a heterodimeric lipid kinase that catalyses the conversion of phosphatidylinositol bisphosphate (PIP2) to phosphatidylinositol trisphosphate (PIP3), which acts as a plasma membrane docking site for proteins that contain a pleckstrin homology (PH) domain. These include the serine/threonine kinases Akt and PDK1 that are key downstream effectors of PI3K action (Fig. 80-2). The PI3K pathway is activated in 30–40% of human cancers and is thought to play a critical role in tumor cell survival, proliferation, growth, and glucose utilization.
The bevacizumab experience suggests that inhibition of the VEGF pathway will be most efficacious when combined with agents that directly target tumor cells. This also appears to be the case in the development of small-molecule inhibitors (SMI) that target VEGF receptor tyrosine kinase activity but are also inhibitory to other kinases that are expressed by tumor cells and important for their proliferation and survival.
Harrison's Internal Medicine Chapter 89. Pancreatic Cancer
Pancreatic Cancer: Introduction
Over 90% of pancreatic cancers are ductal adenocarcinomas of the exocrine pancreas. These tumors occur twice as frequently in the pancreatic head compared to the rest of the organ, and tend to be aggressive, often presenting when locally inoperable or after distal metastases have occurred. Patients with pancreatic cancer have a poor prognosis, with a 5-year survival of only 5%. The discussion of pancreatic cancer here will be limited to ductal adenocarcinomas.
Pancreatic Cancer: Treatment Symptoms and the associated impaired performance status are significant issues in the management of patients with pancreatic cancer, as they can have a marked negative impact on the ability to safely deliver chemotherapy or perform curative surgery. For example, patients with malabsorption secondary to pancreatic insufficiency may be treated with pancreatic enzyme supplementation. Indeed effective symptom management is as important a therapeutic goal as survival prolongation.
Cells respond to environmental cues through a complex and dynamic
network of signaling pathways that normally maintain a critical balance
between cellular proliferation, differentiation, senescence, and death. One
current research challenge is to identify those aberrations in signal transduction
that directly contribute to a loss of this division-limited equilibrium and
the progression to malignant transformation. The study of cell-signaling molecules
in this context is a central component of cancer research.
Potential Biases of Screening Tests The common biases of screening are lead time, length-biased sampling, and selection. These biases can make a screening test seem beneficial when actually it is not (or even causes net harm). Whether beneficial or not, screening can create the false impression of an epidemic by increasing the number of cancers diagnosed. It can also produce a shift in proportion of patients diagnosed at an early stage that improves survival statistics without reducing mortality (i.e.
Oncogene Addiction and Synthetic Lethality The concepts of oncogene addiction and synthetic lethality have spurred new drug development targeting oncogene and tumor-suppressor pathways. As discussed earlier in this chapter and outlined in Fig. 80-3, cancer cells become physiologically dependent upon signaling pathways containing activated oncogenes; this can effect proliferation (i.e.
Palliation Surgery is employed in a number of ways for supportive care: insertion of central venous catheters, control of pleural and pericardial effusions and ascites, caval interruption for recurrent pulmonary emboli, stabilization of cancerweakened weight-bearing bones, and control of hemorrhage, among others. Surgical bypass of gastrointestinal, urinary tract, or biliary tree obstruction can alleviate symptoms and prolong survival. Surgical procedures may provide relief of otherwise intractable pain or reverse neurologic dysfunction (cord decompression).
Breast Cancer: Treatment
Primary Breast Cancer
Breast-conserving treatments, consisting of the removal of the primary tumor by some form of lumpectomy with or without irradiating the breast, result in a survival that is as good as (or slightly superior to) that after extensive surgical procedures, such as mastectomy or modified radical mastectomy, with or without further irradiation. Postlumpectomy breast irradiation greatly reduces the risk of recurrence in the breast.
Table 86-2 5-Year Survival Rate for Breast Cancer by Stage
5-Year Survival, %
Source: Modified from data of the National Cancer Institute—Surveillance, Epidemiology, and End Results (SEER).
Estrogen and progesterone receptor status are of prognostic significance. Tumors that lack either or both of these receptors are more likely to recur than tumors that have them.
Several measures of tumor growth rate correlate with early relapse. S-phase analysis using flow cytometry is the most accurate measure.
administration of adjuvant therapy before definitive surgery and radiation therapy. Because the objective response rates of patients with breast cancer to systemic therapy in this setting exceed 75%, many patients will be "downstaged" and may become candidates for breast-conserving therapy. However, overall survival has not been improved using this approach.
Most recurrences after a surgical resection of a large-bowel cancer occur within the first 4 years, making 5-year survival a fairly reliable indicator of cure. The likelihood for 5-year survival in patients with colorectal cancer is stagerelated (Fig. 87-3). That likelihood has improved during the past several decades when similar surgical stages have been compared. The most plausible explanation for this improvement is more thorough intraoperative and pathologic staging.
Survival by adjuvant chemotherapy. Kaplan-Meier estimates of survival
from the European Study Group for Pancreatic Cancer 1 (ESPAC1) trial for the comparison of adjuvant chemotherapy versus no adjuvant chemotherapy (CT) in patients with resected pancreatic cancer (hazard ratio for death, 0.71; 95% confidence interval, 0.55 to 0.92; p = .009). (Reprinted with permission from JP Neoptolemos, DD Stocken, H Friess, et al: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210, 2004.