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Keywords:

  • cancer;
  • cancer diagnosis;
  • cancer prevention;
  • cancer treatment;
  • history of cancer;
  • National cancer act

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

Tiwari AK, Roy HK (NorthShore University HealthSystem; Evanston, IL, USA). Progress against Cancer (1971–2011): how far have we come? (Historical Perspectives). J Intern Med 2012; 271: 392–399.

Abstract.  ‘The big C’, a common euphemism for cancer, has loomed large on the collective psyche of the mankind for centuries, not least because of the relative dearth of effective treatment against this disease but its ability to relentlessly evade them and come back to haunt us. However, the struggle against cancer took a decisive turn in 1971 when a relentless campaigning by health activists eventually led to signing of the National Cancer Act in the United States, an unprecedented event in the history of diseases. As we commemorate the 40th anniversary of the signing of that historic legislation, an assessment of the progress against cancer would naturally help us understand how we have fared so far in this struggle and guide us in our efforts to re-strategize and re-deploy our limited resources to their best use against this immortal enemy.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

Biologically, cancer represents an abnormal growth of cells that have overcome inhibitory checkpoints owing to sequential accumulation of defects in their DNA [1, 2]; and, by virtue of this inseparable association with our genome, cancer as a disease could probably be as old as our own existence as a species: first documented cases being recorded in Egyptian papyri (2500 BC), which described surface tumours that had ‘no treatment’ available back then. However, much of what we know now about cancer is incredibly recent: as late as 19th century, it was erroneously believed to be a localized manifestation of excessive black bile, caused by melancholia, and was treated by clinicians and quacks alike through bizarre and grotesque ‘remedies’– fire drills, chiselling with knives and scalpels, goat dung, crab paste, frog’s blood, purging, bloodletting and probably worse. Even during most of the twentieth century, available treatment options reflected a fatalistic mindset against cancer; for example, radical surgeries (greatly popularized by William Halsted and his disciples) were aimed at extirpating as much of the diseased organ and its vicinity as possible, and egregious mega-dose chemotherapies were aimed at annihilating any proliferating cell in the body. Unsurprisingly, therefore, during the world-war era, when war was at the heart of most human efforts and effects, the use of military metaphors to describe cancer became a commonality: cancer was thought to be an enemy that ought to be engaged militarily and fought mercilessly. However, there was no official ‘war on cancer’ until 1971 when, yielding to a relentless campaigning by health activists, the US president Richard Nixon signed the National Cancer Act (NCA) that promised the National Cancer Institute (NCI) an unprecedented financial support on a long-term basis [3]. The legislation was initially opposed by many members of the scientific community owing to apprehensions that such an approach, carried out in a constant blaze of publicity, would end up promoting the obvious short-term projects of limited significance at the cost of truly original programmes of basic sciences with no superficial link to cancer [4]. However, although the merits of that legislation have been debated forever, there is no denying the fact that it went a long way in bridging the gap that existed between cancer research and patient care, making sure that the advances in the understanding of cancer were quickly translated into survival benefit for the cancer patients [4, 5]. Nevertheless, it took almost a generation after signing of the legislation before its fruits started appearing in the 1990s in form of a slow but steady decline in cancer mortality in the United States [6–8]. Despite being a national legislation, it affected lives far and beyond the US borders and placed cancer at the forefront of mankind’s struggle against diseases. However, the current US and global cancer statistics that reflect the rising cancer burden worldwide are a stark reminder of the enormity of the task ahead to confront cancer (Fig. 1) [7–11].

image

Figure 1.  Trends in cancer incidence and mortality in the U.S. over past four decades. For about two decades after signing of the National Cancer Act in 1971, no significant improvement was noted in overall cancer mortality rates, albeit situation seemed to have slightly deteriorated, as was by highlighted by John Bailar in 1986 [5]. However, since the early 1990s, the overall cancer death rates have shown consistent statistically significant decreasing trends, and have continued to decrease afterwards, especially for cancers where effective prevention strategies have been implemented [6,7,8]. For example, the cancer death rates for cervical, colorectal and stomach cancers fell by about 60%, 40% and 55% in the U.S. respectively, largely due preventive measures (screening in case of cervical and colorectal cancer, and improved sanitation and effective treatment of H. pylori infection in case of stomach cancer), as opposed to the overall cancer death rates that fell only by about 11% during the same period [7,8]. However, mortality from pancreatic cancer has remained virtually unchanged; that from hepatocellular and intrahepatic bile duct carcinoma has sharply increased; and the incidence of melanoma of skin has more than tripled during past four decades. Unfortunately, the prospects look worse in developing countries [9,10]. However, it’s important to bear in mind that there has been a significant increase in the prevalence of several cancer risk-factors such as obesity, AIDS, hepatitis B and C infections and aging populations during this period; and our improved understanding of their links with cancer and preventive measures against some of them (such as anti-HBV vaccination and anti-retroviral therapy) have definitely prevented several cancers and eventual deaths. Nevertheless, according to the World Health Organization (WHO) estimates based upon current trends, by 2030, there will be 21 million new cancer cases and 13 million cancer deaths each year worldwide, consuming trillions of dollars in patient-care alone [11];clearly, by hook or by crook, cancer still remains undefeated.

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Advances in cancer biology

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

Signing of the legislation acted as a catalyst, especially for innovation and high-performance research with greater potential to be translated into clinical applications. One of the initial paradigm-defining discoveries was that of oncogenic sequences (first was src gene, discovered by Bishop and Varmus), which were initially believed to be present only in viruses, inside normal cells in the 1970s [12]. It truly turned cancer biology on its head: cells did not need to import cancer genes; they had possessed them all along! The search for the origin of cancer then changed from outside to inside the cells, and a horde of endogenous oncogenes and antioncogenes (tumour suppressors) and their signalling pathways were swiftly identified: myc, neu, fos, ras and akt (all oncogenes), and p53, Rb, VHL and APC (all tumour suppressors) [13, 14]. In fact, new cancer-related genes and pathways saw the light of day at such a feverish speed that searching for the origin of cancer inadvertently became akin to solving a complex jigsaw puzzle where finding a new piece (gene or pathway) raised a rather difficult question of where to fit it in the puzzle (carcinogenesis sequence). That is why the work of Vogelstein et al. [15] that identified stepwise activation/inactivation of pathways and associated genetic aberrations during adenoma/carcinoma sequence in patients with colon cancer became so pivotal to understanding of cancer biology. Further delineation of driver mutations (that predispose to cancer) from passenger mutations (relatively innocuous mutations that often correlate with ageing) and about a dozen of key pathways meant that researchers had lesser number of puzzle pieces to worry about [1]. Another remarkable approach was suggested by Hanahan and Weinberg [16]: they proposed that cancers, regardless of origin, share certain hallmark features, and therefore, pathways responsible for imparting those features could indeed be common in different cancers. Discovery of such a stepwise sequence of events during carcinogenesis, possibly implicating three or four of a dozen known cancer-predisposing pathways, for almost all cancers meant that for the first time ever, it became possible to target specific pathways to introduce a wrench in cancer machinery and selectively kill cancer cells. This concept acted as a precursor to several molecular-targeted chemotherapies, as discussed in later sections. During this period, several groundbreaking discoveries were made outside the United States as well, with the discovery of cancer stem cells by a Canadian scientist, John Dick, in mid-1990s being one of them that dully explained how cancer has been able to so successfully evade different drugs and bounce back [17].

The 21st century began with completion of the Human Genome Project that generated a treasure trove of genetic data [18]. The second leg of the project, called the Cancer Genome Atlas, was launched by National Institute of Health (NIH) in 2005 to catalogue genomic changes in all the cancers known to humans: within less than a decade, cancer research moved from Human Genome Project to ‘a project at least 10 000 times bigger when applied to fifty most common human cancers’, as Francis Collins described it [19]. Once completed, it will dwarf the Human Genome Project in terms of the genetic data as well as its scope, and it is speculated that it eventually might transform the very basics of cancer screening, diagnosis, treatment and prevention in coming decades.

Advances in screening and diagnostic approaches

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

After about 25 years of signing of the NCA legislation, when Bailar [6] published his second appraisal of the progress on cancer in 1997-‘Cancer Undefeated’, he made a seminal observation: a significant drop in mortality for colorectal and cervical cancers (30% and 20%, respectively), despite minimal change in overall cancer mortality. Interestingly, both were highly preventable cancers, and screening tests had been in use for them during this period. It then became clearer that spotting signs early will give that extra bit of time to intervene to pre-empt development of cancer and that in essence became the crux of secondary prevention through screening tests: identifying precursor lesions and treating them before their transformation into frank malignancy, just like it is easier to uproot the seedlings than a tree.

Imaging technologies have been at the heart of our advances in identifying precursor lesions. CT scan and MRI in particular have evolved magnificently over this period. In fact, widespread use of CT scan and MRI for imaging studies has been so successful in identifying even small lesions that they often inadvertently create clinical conundrums: many lesions with negligible malignancy potential end up being subjected to potentially harmful treatments, just to exercise caution, especially if present in organs such as pancreas where cancer survival rate is abysmal. Although CT/MRI is not recommended for screening purposes, a recently concluded National Lung Cancer Screening trial found that helical CT screening can reduce cancer deaths amongst smokers by 20% [20]. Endoscopic techniques and instrumentation have largely improved; colonoscopic screening alone, although far from perfect, has been estimated be able to lower mortality from colorectal cancer by 60% [21]. Amongst recent innovations, optical coherence tomography is becoming popular with clinicians because it could detect nonmelanoma skin cancer below the surface of the skin, where standard visual examination cannot see, and provide images interpretable in clinics, in order to weight different treatment options [22].

However, barring few exceptions [such as human papilloma virus (HPV) testing for cervical cancer], one of the notable failures during this period has been the general inability to develop inexpensive and reliable surrogate markers of cancer development and/or progression that can perform consistently in clinical settings. This has marred efforts to risk-stratify the populations for cancer surveillance programmes, resulting in delayed cancer diagnosis and thus high mortality. To alleviate this, the focus is shifting towards novel approaches: for example, detecting field effect through spectroscopic characterization of micro-architectural differences in the histologically normal mucosa, use of a panel of markers (gene expression profiles) detectable in blood, urine or stool, instead of single markers, and detection of circulating tumour cells in blood [23–25]. Furthermore, it is being expected that in future decades, by juxtaposing one’s genome to the Cancer Genome Atlas, it would be possible to identify high-risk cohorts and conduct surveillance in that population.

Advances in cancer treatment

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

Even the most vocal sceptics of the war on cancer now admit that cancer treatment today looks nothing like it did 40 years ago. Combinatorial approach towards cancer, involving localized surgery, chemotherapy and radiotherapy on a case-to-case basis, has largely replaced radical surgeries and highly toxic mega-dose chemotherapies of the past. A 1985 breast cancer treatment trial that demonstrated clear parity of lumpectomy combined with radiotherapy to radical mastectomy was indeed the final nail in the coffin for radical surgeries; they were largely abandoned in favour of other treatment options [26].

Although significant advances have been made in surgical and radiation-related treatments available for patients with cancer, chemotherapy has in particular been at the forefront of these advancements, an irony given the fact that it had in the past been ridiculed as the last hopeless resort for most cancer cases. With discovery of many concealed soft spots inside the cancer cells, focus swiftly shifted to designing targeted therapies that precisely exploited these weaknesses and selectively killed cancer cells. In 1998, when the US Food and Drug Administration (FDA) approved Herceptin (transtuzumab), it became the first oncogene-targeted drug against cancer (in this case, against her2/neu-overexpressing metastatic breast cancer) [27]. The next to follow was Imatinib mesylate (Gleevec) against chronic myeloid leukaemia (CML), which targeted Bcr-abl oncogene located in Philadelphia chromosome, producing long-lasting remissions in more than 95% of patients with CML (Time magazine called it the ‘magic bullet’) [28]. Moreover, when resistance emerged against Gleevec, mostly due to mutations in drug-binding site of the BCR-ABL fusion protein, manufacturers were able to overcome it by using variants of imatinib (such as dasitinib and nilotinib) that could bind to those mutated binding sites [29]. In 2004, FDA approved the use of a new class of anticancer drugs – an angiogenesis inhibitor, Avastin (Bevacizumab; an anti-vascular endothelial growth factor) – for colon cancer chemotherapy [30], and a number of other targeted chemotherapeutics followed the suit: Tarceva [Erlotinib, an anti-epidermal growth factor receptor (anti-EGFR)], Erbitux (Cetuximab; anti-EGFR), Torisel (Temsirolimus; mTOR inhibitor), etc. Most recently in 2011, PLX4032 (targeting BRAF protein) was approved by FDA for use in patients with metastatic melanoma where it was shown to increase survival by about 6 months, unheard survival figures for these patients [31]. Another novel class of anticancer drugs knocking at the doors of cancer clinics is that of cancer therapeutic vaccines that augment the immunogenicity of cancer cells leading to enhanced immune surveillance and killing of cancer cells by immune cells; first of such vaccines – Provenge (sipuleucel-T) – that recently got FDA approval in 2010 is a mixture of patient’s own cells incubated with a protein expressed in 95% of prostate tumours and prolongs life by 4 months in patients with metastatic prostate cancer [32].

Unfortunately, however, cancer has proven to be such a relentless foe, and so remarkable has been its capacity to exploit alternate pathways that resistance has emerged at some point for most chemotherapeutics. To alleviate this, recent proposals have included testing combination of molecular-targeted drugs, which can block alternate escape routes that cancer cells might use to their advantage; for example, emergence of resistance in PLX4032-treated metastatic melanoma patients involved activation of MEK protein, which means that a cocktail of PLX4032 + MEK inhibitor could actually thwart any such effort by cancer cells [33]. However, these approaches are yet to be validated clinically and are complicated by exorbitant costs of these molecular-targeted drugs and the multiplicity of the alternate pathways that cancer cells can activate to evade treatment [34]. In fact, tumour heterogeneity and constant evolution of new genetic mutations in cancer cells make it extremely hard to design any cocktail that could block emergence of resistance all together. Due precisely to above concerns, there has been recent upsurge in the interest in promoting cancer prevention research and greater emphasis on preventive measures.

Advances in cancer prevention

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

In eighteenth century, when a British surgeon, named Percivall Pott, observed a casual correlation between scrotal cancer and soot exposure and recommended protective clothing for chimney cleaners, he was probably amongst the firsts to have believed that cancer is preventable [35]. After Richard Doll’s discovery of carcinogenic effects of smoking in 1950, it took almost quarter of a century for rest of the world to realize the power of primary prevention as a tool against cancer [36]. In 1978, tamoxifen, a selective oestrogen receptor modulator, became the first FDA-approved targeted drug to prevent recurrence in cancer survivors (breast cancer in this case). However, the use of drugs as a prophylaxis against cancer in individuals who never had cancer was unfathomable until mid-1970s, when Michael B. Sporn, a pharmacologist at NIH, together with other researchers, demonstrated the protective effects of retinoids in preclinical models and coined the term ‘chemoprevention’ for it [37]. This inspired several large-scale clinical trials in the United States, especially after NCI founded the Division of Cancer Prevention and Control in 1983, which largely involved nutritional supplements: starting from the Alpha-Tocopherol and Beta-Carotene trial to the more recent Selenium and Vitamin E (prostate) Cancer Prevention Trial (SELECT) [38, 39]. Although the results of these trials were mostly negative-neutral (unfortunately some were harmful too), the main speculations that emerged were that specific supplements could be effective only in a population deficient in that nutrient, creating a new research area of nutrigenetics aimed at identifying such populations [40].

In contrast to nutritional supplements, molecular-targeted chemopreventive drugs achieved considerably more success: tamoxifen against breast cancer (Breast Cancer Prevention Trial) [41]; finesteride, a 5α-reductase inhibitor, against prostate cancer (Prostate Cancer Prevention Trial) [42]; COX-targeted drugs against colon cancer (Adenoma Prevention with Celecoxib (APC) and the Prevention of Colorectal Sporadic Adenomatous Polyps trials) [43, 44]; and hormone replacement therapy (Women’s Health Initiative) [45]. Interestingly, some of these agents had a general protective effect against many different cancers, as recently shown with daily use of aspirin, indicating towards susceptibility of carcinogenesis sequence against drug interventions [46]. However, currently, only tamoxifen and celecoxib are FDA-approved for chemoprevention in all high-risk women and patients with familial adenomatous polyposis, respectively, because unacceptable side effect profile on long-term usage and hence unfavourable risk–benefit ratio hinders the use of most other agents in average-risk populations. To alleviate toxicity-related issues, recent studies have started exploring short-term intermittent treatments (to allow the body to recover without much adverse effects) with drug cocktails for long-term prevention: for example, an intermittent use of a two-drug combination of tumour necrosis factor–related apoptosis-inducing ligand and all-trans-retinyl acetate that work synergistically to induce only precancerous cells to commit suicide, and a low-dose sulindac and difluoromethylornithine cocktail which reduces adenoma occurrence by 70% and advanced adenoma by 90% [47–49]. However, the safety data on the long-term usage of such cocktails in clinical settings are yet to come.

With regard to primary prevention, persistent antitobacco campaigns have led to decreased smoking in Western world (unfortunately, cigarette sales have gone up in developing world during this period) [10], and a better understanding of cancer metabolomics and human physiology has translated into greater emphasis on lifestyle modifications such as balanced diet and exercise to contain the obesity pandemic [50]. Additionally, the development of two cancer prevention vaccines has been a major success: anti-hepatitis B vaccine against hepatocellular carcinoma and anti-HPV vaccine against cervical cancer. Indeed, it is being increasingly acknowledged that primary prevention strategies in form of behavioural modifications such as smoking cessation and obesity control would actually prove to be more successful in reducing the global cancer burden.

Future challenges and recommendations

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

Cancer research had never been more dynamic than the post-1971 period; no other disease has since then been subjected to as much funding, public support and constant scrutiny as cancer. Now, we at least understand that cancer is not alien to our bodies and that cancer cells are just a more perfect version of our own growth as a species, surviving and blossoming as a result of selection over normal cells. Scientific community seems to have reconciled to the fact that as the codes for cancer indeed lie in our very own DNA, any grand plans to annihilate cancer all together are unlikely to be fruitful. Understandably, the strategy against cancer is slowly shifting to become that of containment: detecting malignant/premalignant lesions at the earliest, so that the inevitable confrontation with the widespread malignancy, if early lesions go undetected, could be avoided at any cost. However, this shift in approach towards cancer has not percolated down to the public completely, and that is probably the biggest challenge facing us today: to recalibrate the public expectations and emphasize that their cancer awareness and active participation in preventive measures against cancer are probably the two most crucial factors that can turn the tide against cancer. Ironically though, NCI funding for cancer prevention research has been much lower as compared to cancer treatment research. Only 15–20% of total NCI grants in 1970s–1980s, 20–30% in 1990s and about 10% in 21st century went to prevention-related research, and this reflects the sad realities of the world we all live in: curing cancer is glamorous, prevention is not; a cancer survivor goes on to champion the cause of chemotherapy and pressurizes policymakers to divert resources towards anticancer drug development research; the same cannot be expected from someone who might have benefited from preventive measures against cancer and therefore did not develop cancer in first place. Moreover, chasing of cancer cure by NCI, the escalating cost of modern chemotherapies in treatment-related trials, and long duration and hence high cost associated with prevention trials have made large prevention-related studies unaffordable. Therefore, balancing the distribution of funds between cancer treatment and prevention is definitely another challenge that we need to address effectively.

Nevertheless, prevention strategies have not been foolproof either: barring few exceptions, there is a near-dearth of inexpensive screening tests and powerful biomarkers to risk-stratify the general populations. In that regard, it is being hoped that in coming years, the knowledge of the genetic landscape of tumours and genomic composition of individuals could help create personalized cancer-risk catalogues as a function of their genomic and environmental predispositions to cancer, which in turn would help identify high-risk populations that need to be targeted for surveillance. Currently, even in high-risk cohorts, use of chemopreventive agents is limited because of unacceptable side effects, especially in the presence of other co-morbidities such as in ageing populations that form the bulk of high-risk cohorts. Therefore, although we must continue our efforts to develop new chemotherapies, affordable and accurate screening tests, and least-toxic chemopreventive agents, there is a pressing need to re-emphasize upon primary prevention measures, such as smoking cessation and obesity control. In any case, if we could just hammer home the point that as with most other diseases, an ounce of prevention is worth a pound of cure for cancer too, that alone would be a significant stride forward in our struggle against cancer.

Search strategy and selection criteria

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

References for this Review were identified through searches of PubMed with the following search terms: ‘NCA’, ‘history of cancer’, ‘cancer diagnosis’, ‘cancer treatment’, ‘cancer prevention’ and ‘Human Genome Project’ from 1971 until June 2011. Articles were also identified through searches of the authors’ own files. The final reference list was generated on the basis of relevance to the broad scope of this review, and only articles published in English were reviewed and considered for inclusion in the reference list based upon the further reading opportunity they offered.

Authors contributions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

AK Tiwari planned the manuscript, prepared the first draft and the figure and revised them. HK Roy edited the manuscript, helped in figure preparation and revised the manuscript with AK Tiwari. No medical writer or editor was involved in the manuscript preparation.

Conflict of interest statement

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References

AK Tiwari has no potential conflict of interest to report. HK Roy is a co-founder/shareholder of the American BioOptics, LLC, which has no relevant financial interest or financial conflict with the subject matter or views expressed in the manuscript.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in cancer biology
  5. Advances in screening and diagnostic approaches
  6. Advances in cancer treatment
  7. Advances in cancer prevention
  8. Future challenges and recommendations
  9. Search strategy and selection criteria
  10. Authors contributions
  11. Conflict of interest statement
  12. Acknowledgements
  13. References