The Hallmarks of Cancer

Abstract

and malignant states into invasive cancers (Foulds, 1954). These observations have been rendered more con-Hormone Research Institute University of California at San Francisco crete by a large body of work indicating that the genomes of tumor cells are invariably altered at multiple San Francisco, California 94143 † Whitehead Institute for Biomedical Research and sites, having suffered disruption through lesions as subtle as point mutations and as obvious as changes in Department of Biology Massachusetts Institute of Technology chromosome complement (e.g., Kinzler and Vogelstein, 1996). Transformation of cultured cells is itself a Cambridge, Massachusetts 02142 multistep process: rodent cells require at least two introduced genetic changes before they acquire tumorigenic competence, while their human counterparts are more After a quarter century of rapid advances, cancer redifficult to transform (Hahn et al., 1999). Transgenic search has generated a rich and complex body of knowlmodels of tumorigenesis have repeatedly supported the edge, revealing cancer to be a disease involving dyconclusion that tumorigenesis in mice involves multiple namic changes in the genome. The foundation has been rate-limiting steps (Bergers et al., 1998; see Oncogene, set in the discovery of mutations that produce onco-1999, R. DePinho and T. E. Jacks, volume 18[38], pp. genes with dominant gain of function and tumor sup-5248-5362). Taken together, observations of human pressor genes with recessive loss of function; both cancers and animal models argue that tumor developclasses of cancer genes have been identified through ment proceeds via a process formally analogous to Dartheir alteration in human and animal cancer cells and winian evolution, in which a succession of genetic by their elicitation of cancer phenotypes in experimental changes, each conferring one or another type of growth models (Bishop and Weinberg, 1996). advantage, leads to the progressive conversion of nor-Some would argue that the search for the origin and mal human cells into cancer cells (Foulds, 1954; Nowell, treatment of this disease will continue over the next 1976). quarter century in much the same manner as it has in the recent past, by adding further layers of complexity to a scientific literature that is already complex almost An Enumeration of the Traits beyond measure. But we anticipate otherwise: thoseThe barriers to development of cancer are embodied researching the cancer problem will be practicing a drain a teleology: cancer cells have defects in regulatory matically different type of science than we have expericircuits that govern normal cell proliferation and homeoenced over the past 25 years. Surely much of this change stasis. There are more than 100 distinct types of cancer, will be apparent at the technical level. But ultimately, and subtypes of tumors can be found within specific the more fundamental change will be conceptual.organs. This complexity provokes a number of ques-We foresee cancer research developing into a logical tions. How many dis...

Pathway-gene identification for pancreatic cancer survival via doubly regularized Cox regression

“…Since the plasma membrane ion channels contribute to all basic cellular process [37,38], many ion channels are implicated in the uncontrolled proliferation, decreased apoptosis, and unorganized angiogenesis. According to [37], the ion channels also contribute to the six hallmarks of cancer [39]: "1) self-sufficiency in growth signals, 2) insensitivity to antigrowth signals, 3) evasion of programmed cell death (apoptosis), 4) limitless replicative potential, 5) sustained angiogenesis and 6) tissue invasion and metastasis. "…”

“…• Immune phagocytosis pathway and CYBA gene: One prominent hallmark feature of cancer is the evasion of immune destruction [39]. The immune system is important in preventing tumor initiation and controlling tumor growth through identifying and eliminating the cancer cells (i.e., tumor immune surveillance) [46].…”

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“…In summary, RAS may be highly associated with autoimmune diseases. Genetic influences, such as inflammation status; infections; epigenetic changes; and altered innate, cellular, and humoral immune function, may also play common roles in autoimmune disease and cancer formation 81, 82…”

Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth viaROS‐mediated apoptosis and ATM/ATR–Chk1/Chk2‐regulated cell cycle arrest

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