WCD2016 Special Feature: Subduing the silent killer

In conjunction of April as the international Head and Neck Cancer Month, meet a group of researchers dedicated to reversing nasopharyngeal cancer

By: Syamil Zahari

Photo by: Benny Ang

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ast September, Kuala Lumpur native Voo Chew Wah, 46, and his wife were blissfully one month away from expecting the birth of their fourth child when he felt a swelling on the right side of his neck. He experienced no other symptoms nor felt any discomfort. It could be an inflammation, he thought – easily remedied with some Chinese herbal tea.

The lump, however, never subsided. Sensibly, Voo decided to go to the hospital for a check-up. His doctor immediately noticed a lump at the right side of his nasopharynx, the upper part of the throat just behind the nose. More tests followed. Soon after, his biopsy results came, and the horrifying news was confirmed: Voo had developed a Stage 3 nasopharyngeal cancer.

With that heart-wrenching diagnosis, Voo became another ill-fated number in an alarming nasopharyngeal cancer statistics in Malaysia. Between 900-1,000 Malaysians are diagnosed with nasopharyngeal carcinoma (NPC) every year, according to the National Cancer Registry, making this country the world’s highest in NPC prevalence rate.

Globally, NPC has a distinct geographical distribution that is highly endemic to the countries of Hong Kong, Taiwan, Northern Africa, Alaska, Southeast Asia nations and especially in southern parts of China, predominantly in Guangdong, where the disease is sometimes referred to as ‘Cantonese cancer’ or ‘Kwangtung tumor’ due to high incidence in the region.

In Malaysia, the disease is particularly prevalent in the Chinese community (65%). A higher risk of NPC has also been observed among indigenous groups in East Malaysia, especially the Bidayuhs in Sarawak (2.3-fold higher than the state average). The NPC incidence in males is double than that of females; and the cancer typically affects males aged 30-55, men – husbands and fathers – who are at the prime of their lives.

Lack of attention

Voo’s case underscores the hurdles in the early detection of nasopharyngeal cancer. Dubbed the ‘silent killer’, NPC exhibits few to no indications. Symptoms could be as innocuous as nasal congestion, hearing problems and nosebleeds, all of which could be misdiagnosed as allergies or inflammations. Consequently, as in Voo’s instance, over 70% of in Malaysian cases presented with stage 3 or stage 4 carcinomas.

NPC also affects delicate parts of the head and neck – rendering it virtually inoperable, hence preventing surgical treatment. Furthermore, NPC’s rarity in the Western world and the lack of emphasis placed on NPC studies compared to other globally common types of cancer research such as on breast and lung cancers, all these play a factor in having only 40%-60% of late stage NPC patients surviving beyond five years.

Moreover, these patients often suffer from undesirable side effects of chemoradiotherapy, currently its most recommended treatment, which results in a poor quality of life such as hearing loss due to damaged nerves, or severely parched mouth due to damaged salivary glands, according to Cancer Research Malaysia (formerly known as Cancer Research Foundation, or CARIF).

“In addition, a subset of tumours is resistant to many forms of treatment and recurrent disease has a significant impact on survival rates,” the organization said.

“Therefore, reliable biomarkers for diagnosis, prognosis and treatment for NPC are urgently needed,” it stated.

In an exclusive interview with AMOR Media, Cancer Research Malaysia’s head of Nasopharyngeal Cancer Laboratory Dr Vyomesh Patel said, “What we want to try and develop is something more benched, to experimentally try and understand nasopharyngeal cancer from how it starts and how it rapidly progresses to the point where it is quite fatal to patients.”

He added, “What we want to do is knowing quickly what is wrong, so that the patient could go for a check-up immediately.”

Hence, the goal of the NPC team is improving the most basic understanding of the molecular mechanisms underlying disease initiation and progression, and to use this knowledge to develop markers for the early detection of NPC and novel therapeutic approaches for prevention and treatment, stated Cancer Research Malaysia.

“To this end, our goal aims to develop robust model systems of NPC pathogenesis as well as deciphering the full NPC transcriptome to learn the nature of the genes that get altered in this disease process,” the organization said.

Modelling samples

Recruited to that end, for the past one-and-half year NPC Laboratory research assistant Lee Hui Mei has been diligently gathering tissue samples for testing.

“Our primary aim here,” she said, “because we have the gap of not having a proper model system to study NPC, is to establish a new model system for the NPC.”

Lee explained: “I work together with the ENT surgeon. Whenever he suspects that there’s a patient who has NPC, he will call us. I will collect the tissue samples and then try to process the cells – to grow them in vitro and see whether we can get the epithelial cells.”

One of her biggest difficulties, however, is that the team could not get enough tissue samples. “Currently we only work closely with one clinician,” she said. “We get only one sample per month and that is not enough tissue for us to work with because, as you know, not every tissue sample that you get will be successfully cultured,” she said.

“Obviously, the more samples you have, the higher success rate that you’d get,” she continued. “But so far, we have difficulty engaging with other clinicians.”

Dr Patel agreed. “We have gone to public hospitals and others, but they’ve already agreed to collaborate with the Ministry of Health, so they don’t want to break that link,” he said.

“It’s sort of becoming, not problematic, but more limiting,” he observed. “So the best solution for us is to carry on with what we are doing with the minimum [resources] that we have and try to do the best. ENT surgeons will take us seriously, and other research groups will take us seriously and start helping.”

Another problem that Lee and her team encounter is the difficulty of getting non-malignant tissues. “When the ENT surgeon already suspects that there’s a lump, 90% of the time – when we take the biopsy – the tissue will turn out to be already cancerous,” she said.

“But when you want to develop a treatment, you want to make sure that your drug doesn’t kill normal tissues and instead kills the cancer cells,” she argued.

“So it’s difficult for us to get the normal tissue sample,” she continued. “I don’t think there’s a solution to it. In this field, it’s difficult to obtain healthy tissue. If I ask you to please donate, for a healthy person, you wouldn’t like people to poke in and get your tissues. But it would be also important for scientists to do comparison between malignant and non-malignant tissue,” Lee emphasized.

Disease complexities

Aside from developing the markers of disease progression and novel therapeutic approaches for NPC, one of Cancer Research Malaysia’s current projects is to develop peptide vaccine as treatment option for NPC.

Research associate Chai San Jiun currently works under Dr Patel in the nasopharyngeal cancer research team while also working with Cancer Research Malaysia’s oral cancer research group, both on the peptide vaccine project.

“Previously, we found some targets which are only present in the nasopharyngeal cancer. We have this immunotherapy peptide vaccine that we are testing on nasopharyngeal cancer using in vitro culture of patient’s blood,” she explained.

At the same time, according to Chai, the oral cancer team has also ascertained some likely target genes or biomarkers from oral cancer patients and is also testing the vaccine on those patients. The biomarkers are used to predict treatment response which would allow the researchers to specifically tailor treatment modality for the patients.

“From these biomarkers, we made some small peptide vaccines,” Chai explained. “Previously, we had a few different peptide shots and we are testing which peptide is efficacious. The same thing is going on in the oral cancer research team,” she added.

“So we are combining these peptide vaccines targeting this biomarker in the NPC and oral, and put them together to try to see if we can get a better response in the head and neck cancer patients,” she said.

Nevertheless, despite the fact that genetic alterations in NPC have been studied for some time, current molecular models are still unable to fully explain the complexity of the disease, according to Cancer Research Malaysia.

“[W]e have completed the first genome-wide (more than 15,000 genes) study of Malaysian NPC and identified a number of genes that appear to be important in the development of the disease. NPC cell lines are important model systems for analyzing the complex life cycle and pathogenesis of the Epstein-Barr virus (EBV) as well as for understanding the underlying molecular basis of disease development and progression,” it stated.

While EBV has been linked to nasopharyngeal cancer, “its precise role in the pathogenesis of NPC remains unclear,” explained Cancer Research Malaysia.

“A fuller understanding of the association between EBV and NPC will have relevance to the development of novel therapeutic approaches to target EBV that are also likely to be applicable to other EBV-related cancers,” the organization hoped.

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